Pepsin Enzyme Function | LIVESTRONG.COM Pepsin Enzyme Function Last Updated: May 08, 2015 Kirstin Hendrickson Kirstin Hendrickson is a writer, teacher, coach, athlete and author of the textbook "Chemistry In The World." She's been teaching and writing about health, wellness and nutrition for more than 10 years. She has a Bachelor of Science in zoology, a Bachelor of Science in psychology, a Master of Science in chemistry and a doctoral degree in bioorganic chemistry. A smiling couple eating on a restaurant patio. Photo Credit monkeybusinessimages/iStock/Getty Images Pepsin is an enzyme -- specifically, it's a proteolytic enzyme, meaning it helps digest proteins. Cells in the stomach secrete pepsin to help you digest the protein that you consume in food. Specialized cells in the intestine then absorb the digestion products of the protein into the bloodstream, and your cells take them up from there. Pepsin Chemistry Enzymes, like pepsin, are biological catalysts. This means that they're chemicals that help reactions in the body take place faster than they otherwise would, but they themselves aren't consumed in the reaction.

Specifically, pepsin helps you digest protein. It's secreted by specialized cells in the lining of the stomach called chief cells, explains Dr. Lauralee Sherwood in her book "Human Physiology." Pepsin itself is a protein, but in contrast to the proteins that you eat and digest, pepsin has biological activity in the stomach. Protein Structure Technically, you wouldn't need pepsin to digest the protein that you eat. Proteins are made up of small building block molecules called amino acids, explain Drs. Reginald Garrett and Charles Grisham in their book "Biochemistry." The bonds between amino acids -- called peptide bonds -- break when they're exposed to water and acid. Because your gastric juices are made of mostly water, and the stomach secretes acid, you have all the ingredients you need to digest protein. However, in the absence of pepsin, this reaction would be very slow. Pepsin Formation One of the body's challenges in producing pepsin is keeping it from digesting the cells where it's made. Cells are made up of mostly protein, meaning that if a cell produces pepsin, it's at risk for being digested by the pepsin.

As such, your chief cells produce pepsin in an inactive precursor form, called pepsinogen, explain Drs. Garrett and Grisham. The pepsinogen is activated once it reaches the stomach, so it doesn't harm the cells that produce it. Environment All biological enzymes, pepsin included, function best in a narrow range of temperature and acidity level. Enzymes exposed to environments outside their preferred temperature or acidity -- also called pH -- range don't function. Most body enzymes function best at body temperature and neutral pH, but because pepsin functions in the stomach, it's designed by the cells to work best at very low, or acidic, pH, explain Drs. Mary Campbell and Shawn Farrell in their book "Biochemistry." Types of Bonds In actuality, pepsin can't break all the bonds in a protein molecule. There are many different types of amino acids that are bonded together to make a protein, and pepsin specializes in breaking bonds between very large amino acids. Other proteolytic enzymes, including chymotrypsin and trypsin, work on the bonds between other types of amino acids.

Together, pepsin and the other proteolytic enzymes break the proteins you eat into their constituent amino acids. Related Searches THE LIVESTRONG.COM MyPlate Nutrition, Workouts & Tips GOAL Gain 2 pounds per week Gain 1.5 pounds per week Gain 1 pound per week Gain 0.5 pound per week Maintain my current weight Lose 0.5 pound per week Lose 1 pound per week Lose 1.5 pounds per week Lose 2 pounds per week GENDER Stomach Click to View Pic Stomach The stomach is the main food storage tank of the body. If it were not for the stomach’s storage capacity, we would have to eat constantly instead of just a few times each day. The stomach also secretes a mixture of acid, mucus, and digestive enzymes that helps to digest and sanitize our food while it is being stored. Anatomy of the Stomach Gross Anatomy The stomach is a rounded, hollow organ located just inferior to the diaphragm in the left part of the abdominal cavity. Located between the esophagus and the duodenum, the stomach is a roughly crescent-shaped enlargement of the gastrointestinal tract.

The inner layer of the stomach is full of wrinkles known as rugae (or gastric folds ). Rugae both allow the stomach to stretch in order to accommodate large meals and help to grip and move food during digestion. The stomach can be divided into four regions based on shape and function: The esophagus connects to the stomach at a small region called the cardia. The cardia is a narrow, tube-like region that opens up into the wider regions of the stomach. Within the cardia is the lower esophageal sphincter, a band of muscle tissue that contracts to hold food and acid inside of the stomach. The cardia empties into the body of the stomach, which forms the central and largest region of the stomach. Superior to the body is a dome shaped region known as the fundus. Inferior to the body is a funnel shaped region known as the pylorus. The pylorus connects the stomach to the duodenum and contains the pyloric sphincter. The pyloric sphincter controls the flow of partially digested food (known as chyme) out of the stomach and into the duodenum.

Microscopic Anatomy Microscopic analysis of the stomach’s structure reveals that it is made of several distinct layers of tissue: the mucosa, submucosa, muscularis, and serosa layers. The innermost layer of the stomach is known as the mucosa, and is made of mucous membrane. The mucous membrane of the stomach contains simple columnar epithelium tissue with many exocrine cells. Small pores called gastric pits contain many exocrine cells that secrete digestive enzymes and hydrochloric acid into the lumen, or hollow region, of the stomach. Mucous cells found throughout the stomach lining and gastric pits secrete mucus to protect the stomach from its own digestive secretions. The mucosa of the stomach is much thicker than the mucosa of the other organs of the gastrointestinal tract due to the depth of the gastric pits. Deep inside the mucosa is a thin layer of smooth muscle known as the muscularis mucosae. The muscularis mucosae layer allows the mucosa to form folds and increase its contact with the stomach’s contents. Surrounding the mucosa is the submucosa layer of the stomach. The submucosa is made up of various connective tissues, blood vessels, and nerves.

Connective tissues support the tissues of the mucosa and connect it to the muscularis layer. The blood supply of the submucosa provides nutrients to the wall of the stomach. Nervous tissue in the submucosa monitors the contents of the stomach and controls smooth muscle contraction and secretion of digestive substances. The muscularis layer of the stomach surrounds the submucosa and makes up a large amount of the stomach’s mass. The muscularis is made of 3 layers of smooth muscle tissue arranged with its fibers running in 3 different directions. These layers of smooth muscle allow the stomach to contract to mix and propel food through the digestive tract. The outermost layer of the stomach surrounding the muscularis layer is the serosa – a thin serous membrane made of simple squamous epithelial tissue and areolar connective tissue. The serosa has a smooth, slippery surface and secretes a thin, watery secretion known as serous fluid. The smooth, wet surface of the serosa helps to protect the stomach from friction as it expands with food and moves to mix and propel the food. Physiology of the Stomach Storage In the mouth , we chew and moisten solid food until it becomes a small mass known as a bolus.

When we swallow each bolus, it then passes through the esophagus to the stomach where it is stored along with other boluses and liquids from the same meal. The size of the stomach varies from person to person, but on average it can comfortably contain 1-2 liters of food and liquid during a meal. When stretched to its maximum capacity by a large meal or overeating, the stomach may hold up to 3-4 liters. Distention of the stomach to its maximum size makes digestion difficult, as the stomach cannot easily contract to mix food properly and leads to feelings of discomfort. After the stomach has been filled with food from a meal, it stores the food for about 1-2 hours. During this time, the stomach continues the digestive process that began in the mouth and allows the intestines, pancreas , gallbladder , and liver to prepare to complete the digestive process. At the inferior end of the stomach, the pyloric sphincter controls the movement of food into the intestines. The pyloric sphincter is normally closed to keep food and stomach secretions within the stomach.

Once chyme is ready to leave the stomach, the pyloric sphincter opens to allow a small amount of chyme to pass into the duodenum . This process, known as gastric emptying, slowly repeats over the 1-2 hours that food is stored in the stomach. The slow rate of gastric emptying helps to spread out the volume of chyme being released from the stomach and maximizes the digestion and absorption of nutrients in the intestines . Secretion The stomach produces and secretes several important substances to control the digestion of food. Each of these substances is produced by exocrine or endocrine cells found in the mucosa. The main exocrine product of the stomach is gastric juice – a mixture of mucus, hydrochloric acid, and digestive enzymes. Gastric juice is mixed with food in the stomach to promote digestion. Specialized exocrine cells of the mucosa known as mucous cells secrete mucus into the lumen of the stomach and into the gastric pits. This mucus spreads across the surface of the mucosa to coat the lining of the stomach with a thick, acid- and enzyme-resistant barrier. Stomach mucus is also rich in bicarbonate ions, which neutralize the pH of stomach acid.

Parietal cells found in the gastric pits of the stomach produce 2 important secretions: intrinsic factor and hydrochloric acid. Intrinsic factor is a glycoprotein that binds to the vitamin B12 in the stomach and allows the vitamin to be absorbed in the small intestine . Vitamin B12 is an essential nutrient for the formation of red blood cells. Hydrochloric acid protects the body by killing pathogenic bacteria naturally found in food. Hydrochloric acid also helps to digest proteins by denaturing them into an unfolded shape that is easier for enzymes to digest. The protein digesting enzyme pepsin is activated by exposure to hydrochloric acid inside the stomach. Chief cells, also found within the gastric pits of the stomach, produce two digestive enzymes: pepsinogen and gastric lipase. Pepsinogen is the precursor molecule of the very potent protein-digesting enzyme pepsin. Because pepsin would destroy the chief cells that produce it, it is secreted in its inactive pepsinogen form. When pepsinogen reaches the acidic pH found in the stomach thanks to hydrochloric acid, it changes shape and becomes the active enzyme pepsin.

Pepsin then breaks dietary proteins into their amino acid building blocks. Gastric lipase is an enzyme that digests fats by removing a fatty acid from a triglyceride molecule. G cells are endocrine cells found at the bottom of the gastric pits. G cells release the hormone gastrin into the bloodstream in response to many stimuli, such as signals from the vagus nerve ; the presence of amino acids in the stomach from digested proteins; and the stretching of the stomach wall during a meal. Gastrin travels through the blood to various receptor cells throughout the stomach where it stimulates the glands and muscles of the stomach. Glandular stimulation by gastrin leads to increased secretion of gastric juice to increase digestion. Stimulation of smooth muscles by gastrin leads to stronger contractions of the stomach and the opening of the pyloric sphincter to move food into the duodenum. Gastrin also binds to receptor cells in the pancreas and gallbladder where it increases the secretion of pancreatic juice and bile. Digestion Digestion in the stomach can be divided into 2 classes: mechanical digestion and chemical digestion.

Mechanical digestion is the physical division of a mass of food into smaller masses while chemical digestion is the chemical conversion of larger molecules into smaller molecules. The mixing action of the stomach walls allows mechanical digestion to occur in the stomach. The smooth muscles of the stomach produce contractions known as mixing waves that mix the boluses of food with gastric juice. This mixing leads to the production of the thick liquid known as chyme. While food is being physically mixed with gastric juice to produce chyme, the enzymes present in the gastric juice chemically digest large molecules into their smaller subunits. Gastric lipase splits triglyceride fats into fatty acids and diglycerides. Pepsin breaks proteins into smaller amino acids. The chemical digestion begun in the stomach will not be completed until chyme reaches the intestines, but the stomach prepares hard-to-digest proteins and fats for further digestion. Hormonal control The activity of the stomach is under the control of several hormones that regulate the production of stomach acid and the release of food into the duodenum. Gastrin, produced by the G cells of the stomach itself, increases the activity of the stomach by stimulating increased gastric juice production, muscle contraction, and gastric emptying through the pyloric sphincter.

Cholecystokinin (CCK), produced by the mucosa of the duodenum, is a hormone that acts to slow gastric emptying by contracting the pyloric sphincter. CCK is released in response to food rich in proteins and fats, which are difficult for the body to digest. By inhibiting gastric emptying, CCK allows food to be stored in the stomach longer to promote improved digestion by the stomach and to give the pancreas and gallbladder time to release enzymes and bile to increase digestion in the duodenum. Secretin, another hormone produced by the duodenum's mucosa, responds to the acidity of chyme entering the duodenum from the stomach. Secretin travels through the bloodstream to the stomach where it slows the production of gastric juice by the exocrine glands of the mucosa. Secretin also promotes the production of pancreatic juice and bile that contain acid-neutralizing bicarbonate ions. The net effect of secretin is to protect the intestines from the damaging effects of acidic chyme. Prepared by Tim Taylor, Anatomy and Physiology Instructor Pepsin | world of enzymes and probiotics world of enzymes and probiotics Tweet What is pepsin?

The enzyme named pepsin is released by some chief cells that can be found in the stomach. This enzyme has the capability and the role of degrading food proteins into peptides, thus producing digestion. Discovered in 1836, pepsin was the first revealed enzyme and also the first that was crystallized. Being a digestive protease, the substance is among three main ones that help humans in the digestion process. It works by breaking down dietary proteins and separating them into different components in order for these to be easily absorbed by the intestinal lining. It has a significant role when it comes to human’s digestion process which couldn’t be complete without the existence of it. The digestive enzyme is in fact produced by the precursor substance called pepsiongen that is in the lining of the stomach cells. Pepsin is also produced within these cells, being excreted as a response to the food that enters the digestive tract. Inside the human body pepsin can appear in more than one form, but the most important and active one is pepsin A. Being the main component among all stomach’s juices, this enzyme has many health benefits that makes the human body function properly. The uses of pepsin are mainly connected to preparing antibodies.

The enzyme has a major role in their production, as it helps digest the IgG, which is a substance that cleaves all heavy chains close to the hinge region. Besides this, pepsin is also used in the preparation of collagen for cosmetic purposes. It can additionally be inhibited in 2 different ways. The very first method introduces an inhibitor compound from the pepsin enzyme and the second is to decrease the level of acidity and thus, the enzyme becomes inactive. The process occurs when the pH usually reaches a level of 4 to 5. Regarding the primary benefits of pepsin, scientists have managed to uncover that it can: When does implantation bleeding implantationbleed.com . Digest proteins and breaks them into pieces Stimulate bile secretion Absorb vitamin B12 The supplements and drugs available are over the counter pills and can be taken without medical prescription. Several supplements might or might not have HCI within the capsule. Physicians believe that boosted HCI together with pepsin could help digestion and absorb vitamins and minerals faster.

Health benefits When it comes to health benefits, pepsin can come in handy, as it can be used for a wide variety of health problems, such as: Dyspepsia vomiting caused by morning sickness during pregnancy gastralgia diarrhea cancer treatments As there aren’t any known side effects caused by the usage of this enzyme in the treatment of different ailments, it can be incorporated with confidence in the healing of conditions enumerated above. Nonetheless, a medical specialist has to be always consulted and the treatment with pepsin supplements has to be conducted under medical supervision. If the body doesn’t produce the appropriate amount of pepsin, supplements are highly recommended. As pepsin helps digestion, it’s directly responsible for keeping the human body toxin-free and stimulating the liver to produce bile that leads to the elimination of toxins. Within the stomach, pepsin doesn’t work all the way through in digesting the proteins that enter the body in amino acids. The process of breaking down amino acids is conducted in the small intestine, where pepsin also plays a great role. Being the major element in two main parts of the body and the key factor that prevents the organism from getting intoxicated, this enzyme can’t miss from the organism.

Digestive enzymes | Sciencelearn Hub Digestive enzymes Enzymes are globular proteins that control biological reactions. Digestive enzymes speed up the breakdown (hydrolysis) of food molecules into their ‘building block’ components. These reactions occur outside of the cells lining the gut. Naming and classification of enzymes There are 2 systems used for naming enzymes: The suffix ‘-ase’ is used with the root name of the substance being acted upon, for example, when sucrose (sugar) is digested, it is acted upon by an enzyme called sucrase . The type of chemical reaction involved as the enzyme functions, for example, when sucrase acts on sucrose, it breaks it into a molecule of glucose and a molecule of fructose. This reaction involves adding a water molecule to break a chemical bond and so the enzyme is a hydrolase . All digestive enzymes belong to this hydrolase class. Enzymes are classified according to the type of chemical reaction catalysed. All digestive enzymes are hydrolases, whereas most of the enzymes involved in energy release for muscular contraction are oxidation-reduction enzymes such as oxidases, hydrogenases and dehydrogenases.

Chemical structure of enzymes Enzymes are large protein molecules, all of which have their own specific 3D shape. Embedded within the shape is a region known as the ‘ active site ’, which can attract other suitably shaped molecules to bind to the site. The analogy that is often used to describe this mechanism is that of a key fitting into a lock. The enzyme serves as the lock and the attracted molecule (called the substrate ) is the key. Once the chemical reaction within this lock and key arrangement has been completed, the products are released and the enzyme is free to attract another substrate molecule. The rate of reaction for such a process is thousands of substrate molecules per minute. If a solution of sugar is left in a sealed container, it breaks down into glucose and fructose extremely slowly. In the presence of a small amount of the enzyme sucrase, the rate of breakdown is millions of times faster. Sometimes, chemical substances other than substrates can bind with the active sites of enzymes, blocking their normal function. For example, water-soluble compounds of arsenic and mercury are extremely poisonous because they can permanently bind to some enzyme systems, markedly reducing their efficiency. Depending on the dose , the end result could be death.

Digestive enzymes Digestive enzymes all belong to the hydrolase class, and their action is one of splitting up large food molecules into their ‘building block’ components. Another unique property is that they are extracellular enzymes that mix with food as it passes through the gut. The majority of other enzymes function within the cytoplasm of the cell . The chemical digestion of food is dependent on a whole range of hydrolase enzymes produced by the cells lining the gut as well as associated organs such as the pancreas . The end goal is to break large food molecules into very much smaller ‘building block’ units. These can then be readily and rapidly absorbed through the gut wall and into the bloodstream for transport to the liver and from there to other parts of the body. The main enzyme-producing structures of the human digestive system are the salivary glands , stomach , pancreas, liver and small intestine .

Digestive juices and enzymes What Are the Functions of Amylase, Protease and Lipase Digestive Enzymes | Healthy Eating | SF Gate What Are the Functions of Amylase, Protease and Lipase Digestive Enzymes What Are the Functions of Amylase, Protease and Lipase Digestive Enzymes Digestive enzymes convert food into small molecules. Your digestive system breaks down nutrients you consume in food, converting them into small molecules that your cells, tissues and organs use as fuel and for hundreds of metabolic functions. It takes hours to complete this complex process, which results in simple sugars, fatty acids, glycerol and amino acids. After you break food into small pieces by chewing it, specialized enzymes made in different parts of your digestive tract act on it to finalize the process. Amylase Amylase is a digestive enzyme that acts on starch in food, breaking it down into smaller carbohydrate molecules. The enzyme is made in two places. First, salivary glands in your mouth make salivary amylase, which begins the digestive process by breaking down starch when you chew your food, converting it into maltose, a smaller carbohydrate.

When starchy foods like rice or potatoes begin to break down in your mouth, you might detect a slightly sweet taste as maltose is released. Cells in your pancreas make another type of amylase, called pancreatic amylase, which passes through a duct to reach your small intestine. Pancreatic amylase completes digestion of carbohydrate, producing glucose, a small molecule that is absorbed into your blood and carried throughout your body. Protease Any enzyme that breaks down protein into its building blocks, amino acids, is called a protease, which is a general term. Your digestive tract produces a number of these enzymes, but the three main proteases are pepsin, trypsin and chymotrypsin. Special cells in your stomach produce an inactive enzyme, pepsinogen, which changes into pepsin when it contacts the acid environment in your stomach. Pepsin breaks certain chemical bonds in proteins, producing smaller molecules called peptides and beginning protein digestion. Your pancreas makes trypsin and chymotrypsin, enzymes that are released into your small intestine through the pancreatic duct.

When partially digested food moves from your stomach into your intestine, trypsin and chymotrypsin complete protein digestion, producing simple amino acids that are absorbed into your circulation. Lipase Lipase is an enzyme that breaks down dietary fats into smaller molecules called fatty acids and glycerol. A small amount of lipase, called gastric lipase, is made by cells in your stomach. This enzyme specifically digests butter fat in your food. The main source of lipase in your digestive tract is your pancreas, which makes pancreatic lipase that acts in your small intestine. First, bile made in your liver and released into your intestine converts dietary fat into small fatty globules. Pancreatic lipase, also called steapsin, acts on these fat globules, converting them into fatty acids and glycerol, which are small, energy-dense molecules used by all your cells. Fatty acids and glycerol travel in blood and your lymph vessels to reach all parts of your body. Other Enzymes Although amylase, protease and lipase are the three main enzymes your body uses to digest food, many other specialized enzymes also help in the process.

Cells that line your intestines make enzymes called maltase, sucrase and lactase, each able to convert a specific type of sugar into glucose. Similarly, special cells in your stomach secrete two other enzymes -- renin and gelatinase. Renin acts on proteins in milk, converting them into smaller molecules called peptides, which are then fully digested by pepsin. Gelatinase digests gelatin and collagen, two large proteins in meat, into moderately-sized compounds whose digestion is then completed by pepsin, trypsin and chymotrypsin, producing amino acids. 6. Enzymes • Functions of Cells and Human Body 1. Introduction to the topic of enzymes 2. Mechanism of action and factors affecting enzyme activity 3. Nomenclature of enzymes 5. Use of enzymes in diagnostics 6. Overview of cofactors Introduction to the topic of enzymes Terms and structure There are many different kinds of reactions in biological systems. Attempts to reproduce them outside the living systems (in vitro) revealed, that their speed is significantly lower. In vivo reactions are hundred to million times faster than the same reactions taking place in vitro. A major cause of this difference is the existence of specific catalysts – enzymes.

Enzymes allow the existence of reactions that would not otherwise occur under conditions (temperature, pH, …) present in human body. A catalyst is a substance, which increases the rate of a chemical reaction, but do not alter the chemical equilibrium (only shortens the time until it is achieved). Molecules of enzymes leave reaction unchanged and are not consumed. Enzyme is a specific organic molecule speeding the reaction in biological systems (acting as biocatalyst). It enables reactions to happen under relatively low temperatures, neutral pH and atmospheric pressure, conditions that are common in our bodies. The vast majority of enzymes are proteins (exceptions are some kinds of RNA molecules called ribozymes). Apart from protein component, enzymes can also contain non-protein part. According to its presence, enzymes can be divided into: 1) Simple: containing protein part only (e.g. hydrolases like pepsin, trypsin or ribonuclease) 2) Complex: apart from a protein part called apoenzyme (that is ineffective on its own), they contain a non-protein part as well – called cofactor. Cofactor, together with apoenzyme, forms a biologically active molecule of enzyme – the holoenzyme.

Cofactor may be: 1) Metal ion: Zn2+ (e.g. alcohol dehydrogenase), Mn2+ (e.g. arginase), Fe2+, Cu2+, Mg2+ 2) Organic molecule: very often a derivative of vitamin; according to the nature of its bond with apoenzyme, we further recognise: a) Coenzymes: a non-protein organic molecule that binds to the molecule of apoenzyme freely, and thus can detach from it (e.g. NAD+, NADP+) b) Prosthetic group: a non-protein organic molecule that binds to the molecule of apoenzyme tightly (e.g. heme, FAD) A detailed overview of cofactors and enzymes is listed at the end of this chapter. Enzymes are made up of different number of peptide chains. Even in the case of only one chain, it can contain multiple parts called domains (of same or different enzyme specificity). Enzymes consisting of multiple chains (and thus having quaternary structure) are termed multienzyme complexes. Individual subunits usually have different specificities and are bound non-covalently.

An example of multienzyme complex is the fatty acid synthase, an enzyme catalyzing the synthesis of higher fatty acids in cells. Some enzymes (for example a lot of gastrointestinal enzymes) are produced and stored in their inactive forms termed zymogenes (or proenzymes). The reason is an effort to protect the secretory cells from the autodigestion caused by active forms of the enzymes. Zymogenes are only activated at the place, where their action is desired. Enzymes can be activated, for example, through a process of partial proteolysis, by splitting off a defined portion of the molecule. Let’s look at two examples of this process. The chief cells of the gastric mucosa secrete proenzyme pepsinogene. HCl present in gastric juice helps with the autoactivation of pepsinogen to its active form pepsin. The reaction also takes place autocatalytically, by cleaving the molecules of pepsinogen with already produced pepsin molecules. Similarly to pepsin, the production of trypsin in pancreas starts with its proenzyme trypsinogen.

Enteropeptidase in the small intestine (synthesized by the cells of intestinal mucosa) split off a hexapeptide and thus create an active molecule of trypsin. Isoenzymes and isoforms of enzymes In the organism, there exist enzymes (called isoenzymes) catalysing the same reactions, but differing from each other in their physico-chemical properties (different substrate affinity, KM or sensitivity to inhibitors) and presence in tissues. These differences originate in genetics (isoenzymes have different primary DNA structure) and allow, for example, for a certain regulation of the reactions to be based on the different conditions in different tissues. Very good examples are the isoenzymes catalysing the conversion of glucose to glucose-6-phosphate (a phosphorylation of glucose): glucokinase (located in hepatocytes and pancreatic β-cells) and hexokinase (located in other cells of the body). Glucokinase shows lower affinity for its substrate – glucose (expressed by KM – see further; KM of glucokinase is approximately 10 mmol/l), which means that the enzyme-catalysed reaction takes place only when the level of blood glucose is high enough (mainly after a meal).

In between meals, when the blood glucose is normal, the glucokinase is only slightly active and the liver leaves glucose for other tissues (containing hexokinase with KM value around 0.1 mmol/l). For details see Subchapter 2/9. Apart from isoenzymes, body produces so-called isoforms of enzymes as well. They are multiple forms of enzymes derived from the same gene (so the primary DNA structure is the same), but subjected to different posttranslational modifications or alternative splicing. Resulting from this, isoforms of enzymes can catalyze different reactions. _ Mechanism of action and factors affecting the enzyme activity Enzymes, similar to other catalysts, work by reducing the value of activation energy (see Subchapter 2/4). An enzyme-substrate complex (E-S) forms in the first step of the catalysis. This reaction is usually very fast and reversible. Subsequently, the enzyme catalyses the conversion of a substrate to its product and the complex E-S changes to E-P complex (enzyme-product). E-P complex breaks down and releases the product in a slow and usually irreversible manner. Thus the reaction is divided into several successive steps, which contain one or several E-S transition states.

The activation energies necessary for the process of their synthesis and the conversion of E-S to E-P are lower than the EA involved in the direct conversion of substrate to product, although the overall ΔG of both reactions stays the same. Substrate – enzyme interactions Substrate interacts with the molecule of enzyme in an area called the active site (center). It consists of: 1) Binding site of the enzyme The binding site of the enzyme is small, spatially delimited part of an molecule containing accurately arranged functional groups (-SH, -OH, acidic and basic amino acids) whose position corresponds with the structure of the substrate. The interactions between enzyme and substrate are mostly non-covalent (H- bridges, electrostatic and hydrophobic interactions, van der Waals forces), covalent bonds are rare. 2) Catalytic site The catalytic site contains other groups, which are responsible for the catalytic activity of enzyme. These groups often come from the molecule of cofactor. It is usually difficult to precisely differentiate between binding and catalytic site of the enzyme. Apart from the active site, there can be other sites on the surface of the enzyme called allosteric, which enable the regulation of enzyme through different effectors (inhibitors or activators).

The original model of substrate – enzyme interaction (later named the lock and key theory), created by a German Nobel laureate Emil Fischer at the end of 19th century assumed, that the molecule of substrate fits precisely into the molecule of enzyme. This model was revised in 20th century by American biochemist Daniel Koshland. He assumed that the molecule of substrate is able to induce a conformational change of the binding site (and vice versa). The exact shape of “lock and key” is achieved only after the binding. It appears that this induced fit theory suits the description of the interaction between enzyme and substrate better than the original model. Enzyme specificity Enzyme specificity implies different limitations on the range of action of a particular enzyme. We distinguish: 1) Substrate specificity A substrate specificity means, that an enzyme acts only on a limited range of substrates and cannot catalyze reactions involving other substrate. There are various extents of substrate specificity: a) Absolute Enzyme catalyses the conversion of only one particular substrate, but do not catalyze the conversion of other substrates, even when these are derivatives of the original substrate.

An example is urease, an enzyme catalyzing the reaction: urea + H2O → CO2 + 2 NH3. Urease however, will not catalyze the hydrolysis of methylurea or thiourea. b) Group specificity Represents a more frequent form of substrate specificity, where the enzyme catalyses reactions involving several similar substrates (usually having the same functional groups). The affinity for each substrate can vary (KM for each substrate can be different). As an example we can take carboxypeptidase B, an enzyme hydrolyzing peptides from their carboxy – terminus and preferentially cleaving peptide bonds with charged amino acids (arginine, lysine). 2) Linkage specificity Linkage specificity means that the enzyme will act on a particular type of chemical bond regardless of the rest of the molecular structure. Lipases, for example, are enzymes hydrolyzing different kinds of lipid molecules. Apart from these types of specificity, a lot of enzymes are stereospecific as well, meaning that they only attack certain conformational isomers of substrates (e.g. only L- or only D- form).

It is probably due to the requirement to bind to the substrate at, at least three specific places of the active site of the enzyme (that is a chiral compound) – the other stereoisomere would not bind. Factors affecting the enzyme activity, kinetics of one-substrate reactions Substrate concentration Enzyme kinetics of one-substrate reactions had been studied by Leonor Michaelis and Maud Leonora Menten. Laws of general kinetics, discussed in Chapter 2: Subchapter 4. (concerning equilibrium constant, reaction rate, Gibbs energy), apply here as well. In the case of catalyzed one-substrate reactions we assume that they take place in two steps: where kcat is the reaction rate of the catalyzed reaction. It is also called a turnover number and it indicates the number of molecules of substrate converted by one molecule of enzyme per unit of time (typically one second). The values range from 4.107 (for catalase) till 0,5 (for lysozyme). The maximal reaction rate of the catalyzed reaction can be expressed as: vmax = kcat [E]t where [E]t is the total enzyme concentration.

Michaelis-Menten equation describes the dependence of (initial) velocity v0 on the reaction rate kcat and on the E-S equilibrium as well: v0 = Δ[P] / Δt = = (kcat [E]t [S]) / (KM + [S]) We assume that the amount of enzyme is constant (and its concentration is significantly lower than the concentration of substrate) and we also assume a presence of a certain pseudo-steady state, during which the E-S concentration changes much more slowly than the concentrations of S and P. Substituting the equation (2) to the equation (3) we get: v0 = (vmax [S]) / (KM + [S]) KM (Michaelis constant) is experimentally defined, as the concentration of substrate at which the reaction rate of the enzymatically catalyzed reaction is equal to the half of the maximum rate. KM thus expresses the affinity of substrate and enzyme. The higher the value of KM, the higher the affinity (a lower [S] is necessary to saturate half of the enzyme molecules).

v = vmax / 2 The graph above shows that the dependence of the rate of the enzyme-catalysed reaction on the substrate concentration has a hyperbolic shape. At low substrate concentrations, the curve corresponds to the 1st order kinetics (linear increase). This, almost linear increase, cannot continue indefinitely, due to the limited amount of binding sites on the molecules of enzymes. At sufficiently high substrate concentration, after saturating all available binding sites of all enzyme molecules, a maximal speed (vmax) is reached and remains approximately constant. This part of the curve corresponds to the 0thorder kinetics (the speed is no longer dependent on the substrate concentration). The value of KM can be determined using graphical methods directly from the hyperbolic curve, but it is not often used. The use of reverse values 1/v and 1/[S] (so-called double reciprocal plot according to Lineweaver and Burk) is more accurate. From equation (4): 1/v = (KM + [S]) / (vmax [S]) We can rewrite the equation in the form of a line equation y = a* x + B 1/v =(KM / vmax).

1 / [S] + 1 / vmax Temperature By applying high temperature, enzymes, due to their protein nature, denature (undergo a conformational change that causes the destruction of all, but the primary structure and thus impair the active site as well). Denaturation usually occurs at temperatures around 55-60 °C and causes a drop in or a complete halt of the reaction. Low temperatures, on the other hand, can slow down reactions as well, by reducing the activity of enzymes. There exist a temperature, called the temperature optimum, at which the enzyme has the maximal activity (in the case of majority of the human enzymes it lies around 37 °C). pH (H+ concentration) Similarly to the temperature changes, enzymes are also sensitive to the changes in pH. Extreme values (both low and high) can lead to the denaturation of the enzyme molecules. In addition, the concentration of H+ affects the ionization of acidic and basic groups of the enzyme and substrate. Each enzyme has its pH optimum, which is a value of pH when the enzyme activity is the highest. Activators and inhibitors Other factors affecting the activity of enzymes include activator and inhibitors.

Due to their great importance, we discuss them in a separate section of this chapter. Expressing the enzyme activity In practice, instead of determining the amount of substance or concentration or the enzyme, we measure its catalytic activity. It shows the rate of the reaction under given conditions. Originally, the international unit of enzyme activity (U) had been used. 1 U stands for the amount of enzyme that catalyzes, under standard conditions, the conversion of 1 μmol of substrate in 1 min. Newer unit is katal (kat). 1 katal is the amount of enzyme that, under standard conditions, catalyzes the conversion of 1 mol of substrate in 1 second. However, the unit is too large for practical use. In medicine we mostly use its fractions – microcatal (μkat) – 10-6 kat and nanokatal (nkat) – 10-9 kat. To convert the international unit of enzyme activity to katal, we use the following equation: 1 kat / 6x 107 U.

_ Nomenclature Trivial nomenclature The formerly used term ferments that was based on the fact that enzymes are involved in the process of fermentation, is no longer used. First discovered enzymes were given names according to their source or method of discovery. Their names are therefore without any relation to the reaction mechanism. Many end with –in ending. An example is pepsin, discovered in gastric juices (gr. pepsis – digestion) or ptyalin, found in saliva (gr. ptyalon – saliva). Recommended nomenclature Simpler than systematic nomenclature, but yet being systematic in a way, the recommended nomenclature is often used in routine practice. The name is made by combination of: 1) Substrate + ase: e.g. amylase (catalysing the hydrolysis of amylose) 2) Type of the reaction + ase: e.g. dehydrogenase Systematic nomenclature Systematic nomenclature has been introduced by IUB (International Union of Biochemistry). Every enzyme has its own EC (Enzyme Commission) number, which consists of four digits separated by commas – x.x.x.x.

The first digit denotes one of the six main enzyme classes, second and third stand for a subgroup and a subsubgroup and the last indicates the precise position of enzyme within the subgroup (and thus completely characterises the enzyme). We distinguish the following six major classes of enzymes: 1) Oxidoreductases 6) Ligases (synthetases) 1) Oxidoreductase Oxidoreductases catalyse reactions involving the oxidation of one and the reduction of the other component. They often use cofactors – e.g. NAD+, NADP+, FAD or heme. Examples are: a) Oxidases, peroxidases b) Oxygenases: they bring oxygen molecule into the molecule, either as a -OH group (monooxygenases, also called hydroxylases) or as a O2 (dioxygenases) c) Dehydrogenases: they oxidise the substrate by eliminating H-atoms; they are often abbreviated as DH (e.g.

lactate dehydrogenase – LDH, alcohol dehydrogenase – ADH) d) Desaturases 2) Transferases Transferases participate on the transfer of various groups (amino-, acyl-, methyl-, glycosyl-, phosphoryl-,…) from one molecule to another. Examples are: a) Transaminases (aminotransferases): participate in the transfer of -NH2 group b) Kinases (phosphotransferase): participate in the transfer of phosphate group from ATP (or other nucleoside triphosphates) c) Transaldolases, transketolases 3) Hydrolases Catalyze the hydrolytic reactions (the cleavage of bonds in molecules with the help of water molecule).

Examples are: b) Disaccharidases (saccharase, maltase, lactase) c) Proteases, peptidases (pepsin, trypsin) d) Esterases e) Phosphatases 4) Lyases (synthases) Catalyze the removal of a certain group from the substrate (elimination reaction) by means other than hydrolysis (non-hydrolytic cleavage, for example of bonds between C-C or C-N). They also catalyze additions to the double bond and synthetic reactions without ATP consumptions. Examples are: a) Decarboxylases c) Dehydratases, hydratases 5) Isomerases Catalyse changes within one molecule of substrate (intramolecular changes), so that the product is an isomer of the substrate. Examples are: a) Epimerases: change the position of one –OH group in the molecule b) Mutases: change the position of a phosphate group within the molecule 6) Ligases (synthetases) Catalyse synthetic reactions associated with the ATP hydrolysis (coupling of exergonic and endergonic reactions).

Examples are: _ Enzyme inhibition, importance in pharmacology There are many substances able to affect enzyme function in terms of increase (activators) or decrease (inhibitor) in its activity. The inhibition of enzyme activity is one of the most important regulatory mechanisms in living systems. Apart from these naturally occurring phenomena, the inhibition of specific metabolic pathways underlies the effect of many drugs. It is therefore important to know the mechanism of their inhibition. Based on the reversibility of the effect, there are two main types of inhibition: 1) Reversible Reversible inhibition can be suppressed (or reversed). Inhibitor binds non-covalently (through weak chemical interactions) either to the enzyme’s active site or outside of it. The effect of inhibitor can be eliminated for example through increased supply (concentration) of substrate or through dialysis. a) Competitive Competitive inhibitor competes with the molecule of substrate for the active site of the enzyme. The inhibitor is therefore often structurally similar to the molecule of substrate; it binds to the enzyme, but its unable to undergo enzyme-catalyzed reactions. Increasing the substrate concentration displaces the inhibitor from the active site and thus suppresses its effect.

Competitive inhibitor does not affect vmax, it only delays its attainment (until the inhibitor is displaced by an increased concentration of substrate. KM increases (seemingly, the affinity of an enzyme to substrate is lowered). b) Non-competitive Non-competitive inhibitor binds outside the binding site for substrate (the site of its binding is sometimes referred to as an allosteric site). Through its binding, it changes the conformation of the enzyme to such extent that it affects the conformation of the active site as well, preventing the binding of the substrate. Increasing the substrate concentration does not suppress the inhibition (as the substrate does not bind to the allosteric site, there exist no competition for the binding site). The only way to eliminate the inhibition is to remove the inhibitor (e.g. through dialysis). Because none of the enzyme-inhibitor complexes (or enzyme-inhibitor-substrate complexes) is catalytically active, the amount of enzyme (that would be available to substrate) decreases. That causes a decrease in vmax.KM on the other hand, is not affected. c) Acompetitive In this type of inhibition, the inhibitor binds only to an enzyme-substrate complex creating a ternary complex of enzyme-inhibitor-substrate.

The result is a decrease in both vmax (because the complexes are not enzymatically active) and KM, but their ratio stays the same. Inhibitor has little effectiveness at low substrate concentrations, because there are not enough E-S complexes to which the inhibitor binds. 2) Irreversible Irreversible inhibition involves a covalent modification of the enzyme molecule. Inhibitor covalently binds, either to the active site of the enzyme or outside of it, and thus it is not possible to suppress the inhibition (e.g. by dialysis or by increasing the substrate concentration). Examples are heavy metals (Ag+, Hg2+,…) or organophosphates (or their derivative such as nerve gases sarin or tabun). Another phenomenon is an excess-substrate inhibition. When the concentration of substrate is too high, the individual molecules compete with each other for the active sites. It results in a slight decrease in vmax at high [S]. Allosteric regulation of enzyme activity Many of the “rate-limiting” (or regulatory) enzymes of the metabolism are allosteric. Allosteric regulation of their activity is one of the most important ways to regulate metabolic pathways.

The surface of an allosteric enzyme contains, apart from an active site, other site called allosteric (gr. allos – other) through which it may be affected by modulators (activators or inhibitors). When an allosteric modulator binds to this site it causes a conformational change of the enzyme molecule leading to the change in affinity for substrate or other ligands. Most of the allosteric enzymes are oligomers (they are composed of more subunits). The binding of the modulator to one subunit affects (through conformational change) other subunits as well. We recognize two types of allosteric regulation: 1) Homotropic: modulator functions at the same time as a substrate. A well-known example (though not being an enzyme) is a molecule of O2, which is a homotropic allosteric modulator of hemoglobin. 2) Heterotrophic: modulator and substrate are different molecules. To build on the previous example, CO2 would be a heterotropic allosteric modulator of hemoglobin. Allosteric enzymes show sigmoidal kinetics As an example, we take a reaction affected by a homotropic allosteric activator.

At low concentrations of substrate, the reaction proceeds very slowly, because only a handful of enzyme molecules are occupied by substrate. The turnover occurs, when the enzymes start to have at least one subunit bound to the molecule of substrate (acting as an activator). This also increases the affinity of other subunits to substrate molecules. As seen in figure above, the reaction rate rises sharply at this substrate concentration. The more subunits the enzyme molecule consists of, the sharper is the onset of the effect of increased substrate concentration. Enzyme works according to “all-or-nothing” principle. The reaction almost stops under certain [S], but above it, it quickly achieves vmax (where all binding sites are saturated). This characteristic of the allosteric enzymes is very advantageous, since it allows to quickly “turn on” or “off” the reaction and thus the whole metabolic pathway. _ The use of enzymes in diagnostics Measuring the activity of various enzymes in body fluids is often used in diagnostics to determine the place and extent of tissue damage. Apart from diagnostic contribution, the enzyme activity can give us prognostic information as well (mostly evaluated from the changes in the level of enzymes in time).

We usually measure the enzyme activity directly in the blood plasma: 1) Enzymes specific of the plasma – e.g. coagulation factors 2) Secretory enzymes – that get into the blood in various amounts (e.g. pancreatic amylase or lipase). 3) Intracellular enzymes carrying out different functions within cells. They usually enter the blood after damage to the tissue. When evaluating the levels of enzyme activity, it is important to know their: 1) Intracellular localisation Some enzymes are found only in certain cellular compartments and can therefore act as their markers. For example an enzyme cytochrome oxidase is specific for mitochondria. According to the spectrum of enzymes found in the blood, we can deduce how severe is the damage done to the tissues. If only cytosolic enzymes enter the blood, the impairment is milder than in the case of occurrence of mitochondrial enzymes. 2) Organ and tissue distribution Similar to the distribution of the enzymes in cellular compartments, enzymes differ in their distribution among tissues and organs. Some enzymes are more or less organ specific. These are typically various kinds of isoenzymes or isoforms of enzymes.

An example might be isoenzymes of creatine kinase – CK-MB that is typical for myocardium or CK-MM found in skeletal muscle. The most commonly measured enzymes 1) Liver a) Markers of hepatocytes lesion: 1. ALT (alanine aminotransferase) – located mostly in cytoplasm 2. AST (aspartate aminotransferase) – located mostly in mitochondria AST, as a predominantly mitochondrial enzyme, is released only after more severe damage to the liver cells. According to AST/ALT ratio, we can estimate the extent of the liver damage. b) Markers of cholestasis: 2. GMT (gamma-glutamyltransferase) – increased activity is also present in chronic alcoholic liver lesions.

2) Pancreas a) Pancreatic amylase –less specific than lipase b) Pancreatic lipase 3) Muscle tissue To distinguish between the possible sites of lesion we measure the activity of the creatin kinase isoenzymes: a) CK-MM – found in skeletal muscle b) CK-MB – found in myocardium c) CK-BB – found in brain Apart from assessing the CK-MB levels, in the case of myocardial infarction, we measure the levels of following enzymes: a) Troponin I and T, which are currently the most specific markers of cardiac damage. Their concentration rises approximately 12 hours after infarct. b) Myoglobin, which is less specific, but achieves its peak concentration in blood already 2 hours after a heart attack. 4) Bone tissue a) ALP (alkaline phosphatase) – located in osteoblasts (so-called bone fraction), but also in liver (so-called liver fraction), GIT or kidney cells.

b) ACP (acid phosphatase) – located in osteoclasts and prostate cells Other diagnostic enzymes include: 1) Lactate dehydrogenase isoenzymes (LD, LDH) a) LD-1 – found in cardiomyocytes and erythrocytes b) LD-2 – found in RES c) LD-3 – found in lungs d) LD-4 – found in kidneys, pancreas and placenta e) LD-5 – found in liver and skeletal muscle Enzyme pepsin | biochemistry | Britannica.com biochemistry Pepsin, the powerful enzyme in gastric juice that digests proteins such as those in meat, eggs, seeds, or dairy products. Chief cells (C) in the stomach synthesize and secrete pepsinogen, which mixes with hydrochloric … Uniformed Services University of the Health Sciences (USUHS) Pepsin was first recognized in 1836 by the German physiologist Theodor Schwann . In 1929 its crystallization and protein nature were reported by American biochemist John Howard Northrop of the Rockefeller Institute for Medical Research .

(Northrop later received a share of the 1946 Nobel Prize for Chemistry for his work in successfully purifying and crystallizing enzymes.) Glands in the mucous-membrane lining of the stomach make and store an inactive protein called pepsinogen. Impulses from the vagus nerve and the hormonal secretions of gastrin and secretin stimulate the release of pepsinogen into the stomach, where it is mixed with hydrochloric acid and rapidly converted to the active enzyme pepsin. The digestive power of pepsin is greatest at the acidity of normal gastric juice (pH 1.5–2.5). In the intestine the gastric acids are neutralized (pH 7), and pepsin is no longer effective. In the digestive tract pepsin effects only partial degradation of proteins into smaller units called peptides , which then either are absorbed from the intestine into the bloodstream or are broken down further by pancreatic enzymes. Small amounts of pepsin pass from the stomach into the bloodstream, where it breaks down some of the larger, or still partially undigested, fragments of protein that may have been absorbed by the small intestine.

Chronic backflow of pepsin, acid, and other substances from the stomach into the esophagus forms the basis for reflux conditions, particularly gastroesophageal reflux disease and laryngopharyngeal reflux (or extraesophageal reflux). In the latter, pepsin and acid travel all the way up to the larynx , where they can cause damage to the laryngeal mucosa and produce symptoms ranging from hoarseness and chronic cough to laryngospasm (involuntary contraction of the vocal cords ) and laryngeal cancer . Pepsin is prepared commercially from swine stomachs. Crude pepsin is used in the leather industry to remove hair and residual tissue from animal hides prior to their being tanned. It is also used in the recovery of silver from discarded photographic films by digesting the gelatin layer that holds the silver compound . Learn More in these related articles: Digestion Big Ideas Digestion Digestion is the breakdown of food into simpler molecules that can be absorbed by the body. The digestive system is actually a long hollow tube called the gastrointestinal tract, or GI tract.

The digestive system includes the mouth, pharynx, esophagus, stomach, small intestine, and large intestine. Several major glands include the salivary glands, the pancreas, and the liver. The first task of the digestive system is to break down food into a fine pulp (mechanical digestion). When the food is physical broken down, digestive chemicals break the food down into small molecules (chemical digestion). The mouth is the organ in which the process of digestion begins. It starts the process of mechanical digestion by grinding the food with teeth. Also in the mouth, an enzyme called salivary amylase begins to break down long starch molecules into maltose. Once the food is ready to be swallowed it is gathered into a ball called a bolus and sends to the part of the bolus called the pharynx. Once in the pharynx, the bolus next passes down the esophagus. The bolus is moved down the esophagus by rhythmic muscles contracts called peristalsis. At the end of the esophagus is a thick ring of a muscle called a sphincter which allows food to enter the stomach but not from the stomach back into the esophagus.

Once the food enters the stomach it is mixed with the digestive juices. The stomach produces stomach acid; hydrochloric acid, and pepsin. Stomach acid activates the pepsin that digests protein into smaller proteins. Proteins are long chains of amino acids that are essential for cell growth and repair. Next, from the stomach the food moves into the small intestine where it continues to be digested by enzymes produced in the pancreas. In the small intestine, the pancreas empties digestive juices that break down carbohydrates, fats, and protein. The liver produces bile that is stored in the gallbladder between meals and emptied into the small intestine. The small intestine is where most of the nutrients are absorbed and thus is the most important organ in the digestive system. The undigested materials continue to the large intestine where the remaining water is absorbed and eventually the waste material is expelled through the rectum. Also, fats (lipids) are molecules that are stored for future energy uses mainly because they are difficult to digest.

EPE Stomach, Gallbladder and Pancreas | Interactive Anatomy Guide Home > Digestive System > Digestive System of the Lower Torso > Stomach, Gallbladder and Pancreas Stomach, Gallbladder and Pancreas The stomach, gallbladder, and pancreas are three of the most important digestive organs in the human body. These organs work together to produce and store secretions that digest our food into its most basic building blocks. Once digested, these small molecules pass into our intestines to be absorbed and to feed our body’s tissues. These three major organs also produce hormones that help to coordinate their functions and even lead to the feeling of fullness after consuming a meal.... Move up/down/left/right: Click compass arrows Rotate image: Click and drag in any direction, anywhere in the frame Identify objects: Click on them in the image Full Stomach, Gallbladder and Pancreas Description [Continued from above] . . .

Anatomy of the Stomach, Gallbladder, and Pancreas Stomach A hollow muscular organ about the size of 2 closed fists, the stomach is located inferior to the diaphragm and lateral to the liver on the left side of the abdominal cavity. The stomach forms part of the gastrointestinal tract between the esophagus and the duodenum (the first section of the small intestine). The wall of the stomach contains several layers of epithelium, smooth muscle, nerves, and blood vessels. The innermost layer of the stomach is made of epithelium containing many invaginations known as gastric pits. The cells of the gastric pits produce gastric juice - an acidic mixture of mucus, enzymes and hydrochloric acid. The hollow portion of the stomach serves as the storage vessel for food before it moves on to the intestines to be further digested and absorbed. At the inferior end of the stomach is a band of smooth muscle called the pyloric sphincter. The pyloric sphincter opens and closes to regulate the flow of food into the duodenum. Gallbladder The gallbladder is a 3-inch long pear-shaped sac located on the posterior border of the liver.

Connected to the bile ducts of the liver through the cystic duct , the gallbladder receives bile transported from the liver for storage on a regular basis to prepare for the digestion of future meals. During digestion of a meal, smooth muscles in the walls of the gallbladder contract to push bile into the bile ducts that lead to the duodenum. Once in the duodenum, bile helps with the digestion of fats. Pancreas The pancreas is a 6-inch long heterocrine gland located inferior to the stomach and surrounded by the duodenum on its medial end. This organ extends laterally from the duodenum toward the left side of the abdominal cavity, where it tapers to a point. The pancreas is considered a heterocrine gland because it has both endocrine and exocrine gland functions. Small masses of endocrine cells known as pancreatic islets make up around 1% of the pancreas and produce the hormones insulin and glucagon to regulate glucose homeostasis in the blood stream. The other 99% of the pancreas contains exocrine cells that produce powerful enzymes that are excreted into the duodenum during digestion.

These enzymes together with water and sodium bicarbonate secreted from the pancreas are known as pancreatic juice. Physiology of the Stomach, Gallbladder, and Pancreas Digestion The stomach, gallbladder, and pancreas work together as a team to perform the majority of the digestion of food. Food entering the stomach from the esophagus has been minimally processed – it has been physically digested by chewing and moistened by saliva, but is chemically almost identical to unchewed food. Upon entering the stomach, each mass of swallowed food comes into contact with the acidic gastric juice, which contains hydrochloric acid and the protein-digesting enzyme pepsin. These chemicals begin working on the chemical digestion of the molecules that make up the food. At the same time, the food is mixed by the smooth muscles of the stomach wall to increase the amount of contact between the food and the gastric juice. The secretions of the stomach also continue the process of moistening and physically softening the food until the food becomes an acidic semi-liquid material known as chyme. At this point, the stomach begins to push the chyme through the pyloric sphincter and into the duodenum.

In the duodenum , the bulk of digestion is completed thanks to the preparation of chyme by the stomach and the addition of secretions from the gallbladder and pancreas. Bile from the gallbladder acts as an emulsifier to break large masses of fats into smaller masses. Pancreatic juice contains bicarbonate ions to neutralize the hydrochloric acid of chyme. Enzymes present in the pancreatic juice complete the chemical digestion of large molecules that began in the mouth and stomach. The completely digested food is then ready for absorption by the intestines . Storage The stomach, gallbladder, and pancreas all function together as storage organs of the digestive system. The stomach stores food that has been ingested and releases it in small masses to the duodenum. The release of small masses of food at a time improves the digestive efficiency of the intestines, liver, gallbladder, and pancreas and prevents undigested food from making its way into feces. As they are accessory organs of the digestive system, the gallbladder and pancreas have no food passing through them. They do, however, act as storage organs by storing the chemicals necessary for the chemical digestion of foods.

The gallbladder stores bile produced by the liver so that there is a sufficient supply of bile on hand to digest fats at any given time. The pancreas stores the pancreatic juice produced by its own exocrine glands so that it is prepared to digest foods at all times. Secretion The stomach, gallbladder, and pancreas all share the common function of secretion of substances from exocrine glands. The stomach contains 3 different exocrine cells inside of its gastric pits: mucous cells, parietal cells, and chief cells. Mucous cells produce mucus and bicarbonate ion that cover the surface of the stomach lining, protecting the underlying cells from the damaging effects of hydrochloric acid and digestive enzymes. Parietal cells produce hydrochloric acid to digest foods and kill pathogens that enter the body through the mouth. Chief cells produce the protein pepsinogen that is turned into the enzyme pepsin when it comes into contact with hydrochloric acid. Pepsin digests proteins into their component amino acids. The mixture of mucus, hydrochloric acid, and pepsin is known as gastric juice. Gastric juice mixes with food to produce chyme, which the stomach releases into the duodenum for further digestion.

The gallbladder stores and secretes bile into the duodenum to aid in the digestion of chyme. A mixture of water, bile salts, cholesterol, and bilirubin, bile emulsifies large masses of fats into smaller masses. These smaller masses have a higher ratio of surface area to volume when compared to large masses, making it easier for them to be digested. The pancreas stores and secretes pancreatic juice into the duodenum to complete the chemical digestion of food that began in the mouth and stomach. Pancreatic juice contains a mixture of enzymes including amylases, proteases, lipases, and nucleases. Carbohydrates entering the small intestine are broken down into monosaccharides by enzymes such as pancreatic amylase, maltase, and lactase. Proteins in the duodenum are chemically digested into amino acids by pancreatic enzymes such as trypsin and carboxypeptidase. Pancreatic lipase breaks triglycerides into fatty acids and monoglycerides. The nucleic acids DNA and RNA are broken down by nucleases into their component sugars and nitrogenous bases.

Hormones Several hormones are used to regulate the functions of the stomach, gallbladder, and pancreas. The hormones gastrin, cholecystokinin, and secretin are secreted by organs of the digestive system in response to the presence of food and change the function of the stomach, gallbladder, and pancreas. Our pancreas produces the hormones insulin and glucagon to affect the behavior of cells throughout the body. Gastrin is a hormone produced by the walls of the stomach in response to the filling of the stomach with food. Food stretches the stomach walls and raises the normally acidic pH of the stomach. G cells in the gastric glands of the stomach respond to these changes by producing gastrin. G cells release gastrin into the blood where it stimulates the exocrine cells of the stomach to produce gastric juice. Gastrin also stimulates smooth muscle tissue of the gastrointestinal tract to increase the mixing and movement of food. Finally, gastrin relaxes the smooth muscles that form the pyloric sphincter, causing the pyloric sphincter to open. The opening of the pyloric sphincter allows food stored in the stomach to begin entering the duodenum for further digestion and absorption in the intestines.

Cholecystokinin (CCK), a hormone produced in the walls of the small intestine , is released into the bloodstream in response to the presence of chyme in the intestine that contains high levels of proteins and fats. Proteins and fats are more difficult for the body to digest than carbohydrates are, so CCK is important in making changes to the digestive system to handle these types of foods. CCK travels through the bloodstream to the stomach, where it slows the emptying of the stomach to give the intestines more time to digest the protein- and fat-rich chyme. CCK also stimulates the gallbladder and pancreas to increase their secretion of bile and pancreatic juice to improve the digestion of fats and proteins. Finally, CCK is detected by receptors in the satiety center of the hypothalamus that control the feeling of hunger. The satiety center reads the presence of CCK as an indication that the body is no longer hungry for food. Secretin is another hormone produced by the intestinal walls, but unlike CCK, it is produced in response to the acidity of chyme that the stomach releases into the duodenum.

Secretin flows through the bloodstream to the stomach, where it inhibits the production of hydrochloric acid by parietal cells. Secretin also binds to receptors in the gallbladder and pancreas, stimulating them to secrete increased amounts of bile and pancreatic juice. Sodium bicarbonate present in pancreatic juice neutralizes the acidity of the chyme to prevent damage to the walls of the duodenum and provides a neutral pH environment for the digestion of chyme. Insulin is a hormone produced by the beta cells of the pancreatic islets of the pancreas. The pancreas produces insulin in response to the presence of high levels of glucose in the blood. Insulin stimulates cells, particularly in the liver and skeletal muscles , to absorb glucose from the blood and use it as an energy source or store it as glycogen. Insulin also stimulates adipocytes to absorb glucose to build triglycerides for energy storage. Our body produces higher levels of insulin following a meal in order to remove glucose molecules from the blood before they can reach high concentrations and become toxic to the body’s cells. Glucagon is a hormone produced by the alpha cells of the pancreatic islets of the pancreas.

Glucagon acts as an antagonist to insulin by stimulating the release of glucose into the bloodstream to raise blood glucose levels between meals. Hepatocytes in the liver store glucose in large macromolecules known as glycogen. Glucagon binding to receptors on hepatocytes triggers the breakdown of glycogen into many glucose molecules, which are then released into the bloodstream. Prepared by Tim Taylor, Anatomy and Physiology Instructor

Question: The enzyme pepsin is released by cells in which part of the human body?
Answer: Stomach