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In three steps, we form that acetocoenzyme A.
Pyruvate Decarboxylation .txt
But the final step is needed to not only regenerate that Lipomi coenzyme, but also generate that NADH as well as that H ion.
Pyruvate Decarboxylation .txt
So this is a step that by which we essentially prepare that pyruvate molecule.
Pyruvate Decarboxylation .txt
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.
Pyruvate Decarboxylation .txt
And now we can basically take this acetyl and give it to the citric acid cycle.
Pyruvate Decarboxylation .txt
So now let's actually take a look at the individual steps that help us generate fatty acid molecules.
Fatty Acid Synthesis .txt
Now as we look at all these different steps, keep in mind that all of them take place in the cytoplasm of our cell.
Fatty Acid Synthesis .txt
Now let's briefly recall what happened in the previous several lectures.
Fatty Acid Synthesis .txt
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.
Fatty Acid Synthesis .txt
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.
Fatty Acid Synthesis .txt
So let's assume that actually took place.
Fatty Acid Synthesis .txt
So we have the fecal coenzyme A molecule and it's found in the cytoplasm of that cell.
Fatty Acid Synthesis .txt
What happens next?
Fatty Acid Synthesis .txt
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.
Fatty Acid Synthesis .txt
And what that means is we're going to commit the CETL Co enzyme A molecule, to actually undergoing fatty acid synthesis.
Fatty Acid Synthesis .txt
And this is the step that commits the CETL Co enzyme A to helping form that fatty acid chain.
Fatty Acid Synthesis .txt
So let's see what the step actually consists of.
Fatty Acid Synthesis .txt
So firstly, the enzyme that catalyzed this step is a carboxylase.
Fatty Acid Synthesis .txt
More specifically, it's acetylco enzyme A carboxylase.
Fatty Acid Synthesis .txt
And just like any other carboxylase, this carboxylase requires three different things.
Fatty Acid Synthesis .txt
Number one is it means an energy source and that's where ATP comes into play.
Fatty Acid Synthesis .txt
Number two is it means a carbon source.
Fatty Acid Synthesis .txt
Why?
Fatty Acid Synthesis .txt
Well, because as this name applies, the carboxylase will actually attach a carbon dioxide onto the ceiling.
Fatty Acid Synthesis .txt
Co enzyme A molecule, elongating this molecule by one carbon.
Fatty Acid Synthesis .txt
And that's why we have the bicarbonate.
Fatty Acid Synthesis .txt
Number three is attached.
Fatty Acid Synthesis .txt
Covalently onto the carboxylase is biotin and biotin is a vitamin B seven molecule.
Fatty Acid Synthesis .txt
Now, the reaction as shown on the board is actually the sum of two individual reactions.
Fatty Acid Synthesis .txt
So this is actually the overall net reaction of the sum of two different reactions that are not shown on the board.
Fatty Acid Synthesis .txt
But I'd like to talk about them for just a moment because they actually demonstrate the importance of biotin.
Fatty Acid Synthesis .txt
So what happens in step number one in this reaction?
Fatty Acid Synthesis .txt
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.
Fatty Acid Synthesis .txt
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.
Fatty Acid Synthesis .txt
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.
Fatty Acid Synthesis .txt
So that's the importance of biotin.
Fatty Acid Synthesis .txt
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.
Fatty Acid Synthesis .txt
Now this step is very important for three reasons.
Fatty Acid Synthesis .txt
Number one is it commits the CETO coenzyme A molecule.
Fatty Acid Synthesis .txt
Number two is it's the rate limiting step.
Fatty Acid Synthesis .txt
And number three is this is the enzyme that is regulated to basically either inhibit or activate fatty acid synthesis.
Fatty Acid Synthesis .txt
Now, we're not going to focus on the regulation of this enzyme because that's actually pretty complicated.
Fatty Acid Synthesis .txt
So we'll save that discussion for a later lecture.
Fatty Acid Synthesis .txt
So remember three things about this step.
Fatty Acid Synthesis .txt
Number one is it commits the molecule.
Fatty Acid Synthesis .txt
Number two is it's a regulatory step?
Fatty Acid Synthesis .txt
Number three is it's a rate limiting step?
Fatty Acid Synthesis .txt
And we'll come back to this step when we'll look at step number four.
Fatty Acid Synthesis .txt
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.
Fatty Acid Synthesis .txt
Now, the enzyme that catalyzes steps one through step seven is fatty acid syntax.
Fatty Acid Synthesis .txt
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.
Fatty Acid Synthesis .txt
And the ACP domain stands for Acyl carrier protein.
Fatty Acid Synthesis .txt
Remember, the Acyl carrier protein actually contains a phosphate group and that group contains this sulf hydro group.
Fatty Acid Synthesis .txt
And that will allow the binding of certain molecules as we'll see in just a moment.
Fatty Acid Synthesis .txt
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.
Fatty Acid Synthesis .txt
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.
Fatty Acid Synthesis .txt
So step number one is catalyzed by one of the catalytic domains we call acetil transasilise and that is found on this FAS molecule.
Fatty Acid Synthesis .txt
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.
Fatty Acid Synthesis .txt
In addition, we kick off the coenzyme A as shown here.
Fatty Acid Synthesis .txt
Now, this acetyl coenzyme A is not the same as this acetyl Co enzyme A.
Fatty Acid Synthesis .txt
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.
Fatty Acid Synthesis .txt
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.
Fatty Acid Synthesis .txt
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.
Fatty Acid Synthesis .txt
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.
Fatty Acid Synthesis .txt
Now, once we form that, what happens next?
Fatty Acid Synthesis .txt
Well, in the next step, this is where the melanoc coenzyme A comes into play.
Fatty Acid Synthesis .txt
So the melanoco enzyme A that we form in this step now is a reactant in step number three.
Fatty Acid Synthesis .txt
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.
Fatty Acid Synthesis .txt
And so we generate this intermediate.
Fatty Acid Synthesis .txt
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.
Fatty Acid Synthesis .txt
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.
Fatty Acid Synthesis .txt
In fact, this domain here can actually bind other carbon molecules.
Fatty Acid Synthesis .txt
In fact, it can bind proponel coenzyme A.
Fatty Acid Synthesis .txt
And that's how we're able to actually form odd chain fatty acid molecules.
Fatty Acid Synthesis .txt
But in this case, we're only going to focus on the even chain fatty acid molecules.
Fatty Acid Synthesis .txt
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.
Fatty Acid Synthesis .txt
This enzyme domain is highly specific for the malcoenzyme A, unlike this catalytic domain that is not that specific for this acetyl group.
Fatty Acid Synthesis .txt
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.
Fatty Acid Synthesis .txt
So let's take a look at step four.
Fatty Acid Synthesis .txt
Now, step four is a very important step.
Fatty Acid Synthesis .txt
Why?
Fatty Acid Synthesis .txt
Well, because this is a step that actually drives this entire reaction forward.
Fatty Acid Synthesis .txt
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.
Fatty Acid Synthesis .txt
Now, what we do here is a decarboxylation step, and we break a thio ester bond.
Fatty Acid Synthesis .txt
And this pretty much releases enough energy for us to actually drive this reactant forward.
Fatty Acid Synthesis .txt
So this step is a crucial step in fatty acid synthesis because it drives the overall reaction forward.
Fatty Acid Synthesis .txt
What happens is the enzyme acyl, malno ACP condensing enzyme, basically decarboxylates this group, and that prepares these two molecules for nucleophilic attack.
Fatty Acid Synthesis .txt
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.
Fatty Acid Synthesis .txt
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.
Fatty Acid Synthesis .txt
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.
Fatty Acid Synthesis .txt
This bond here and the product of this is aceto, acetyl attached onto the ACP molecule.
Fatty Acid Synthesis .txt
So this is what we call the condensation step.
Fatty Acid Synthesis .txt
Now, notice what else this step actually tells us.
Fatty Acid Synthesis .txt
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.
Fatty Acid Synthesis .txt
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.
Fatty Acid Synthesis .txt
So carbon dioxide is ultimately removed from that fatty acid chain.
Fatty Acid Synthesis .txt
It does not contribute to those carbon atoms.
Fatty Acid Synthesis .txt
So, again, very important step because it allows us to drive the equilibrium of this reaction toward the product side.
Fatty Acid Synthesis .txt
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.
Fatty Acid Synthesis .txt
Now, let's move on to step number five.
Fatty Acid Synthesis .txt