When food gets down to the stomach as a result of the peristaltic action of the oesophagus, it is acted upon by gastric juice which is secreted by the gastric glands situated in the thick walls of the stomach. Gastric juice contains two main enzymes: pepsin and rennin. Pepsin breaks down proteins into short polypeptide chains while rennin coagulates the soluble milk protein, casein forming an insoluble curd which is subsequently attacked by pepsin.
Pepsin which is secreted as an inactive precursor known as Pepsinogen. Pepsinogen is activated by hydrochloric acid and by pepsin itself which makes the reaction autocatalytic. Pepsin is secreted in a inactive form because it is a proteolytic enzyme and might attack the tissues before been released. It is activated by some of its amino acids that is being split off at one end of the proteolytic chain. Once secreted the active form of pepsin is prevented from attacking the tissues by the mucus lining the stomach wall.
Hydrochloric acid does not only activate the pepsinogen but also provides the best pH for the functioning of the enzyme. Hydrochloric acid is secreted by special oxyntic cells located in the deeper regions of the gastric glands giving the gastric juice a pH of less than 2.0
Pavlov in his experiments showed what triggers the production of gastric juice. Pavlov’s classical experiments on the digestion in dogs showed that gastric juice just like saliva will be secreted as a result of sight, smell, taste or expectation of food. Although, these secretions is nothing compared to the copious flow of gastric juice when the food arrives in the stomach which is due largely to the chemical and mechanical stimulation of the stomach lining and the actions of a hormone called gastrin. Gastrin circulates in the blood and causes the gastric glands to secrete hydrochloric acid.
As all these takes place, the rhythmical contractions of the stomach form the food into a semi-solid substance known as chime.
Mechanism of the Production of Hydrochloric Acid by the Oxyntic cells
The production of hydrochloric acid by the oxyntic cells is indeed a remarkable process and closely resembles that way carbon(iv)oxide is carried in the red blood cells. Inside the oxyntic cells, the enzyme known as carbonic anhydrase catalyses the formation of carbonic acid from carbon(iv)oxide and water and the carbonic acid produced dissociates into bicarbonate ions and hydrogen ions(H+). The Hydrogen ions then combines with chloride ions(Cl-), formed from the dissociation of sodium chloride, to form hydrochloric acid which is then secreted by the cell.
There is then a massive movement of bicarbonate ions out of the cell I to the surrounding blood capillaries giving rise to a phenomenon known as ‘Alkaline Tide’.
The stomach begins the digestion of food by squeezing and churning it and secreting a liquid mixture called gastric juice. This consists of water, hydrochloric acid, enzymes, and mucus. It also contains the protein-digesting enzyme pepsin.
Cells in the stomach lining, called chief cells, secrete pepsin in an inactive form called pepsinogen. Impulses from the vagus nerve and hormones like gastrin stimulate these cells to secrete hydrochloric acid that lowers the pH of the gastric juice. This low pH activates the pepsinogen into the active enzyme pepsin.
Functional Roles of Gastric Juice and Pepsin
The acidic gastric juice secreted by the parietal cells in the stomach contains several enzymes that aid in chemical digestion and in the breakdown of proteins. Hydrochloric acid activates pepsinogen which is converted to the active digestive enzyme, pepsin, which digests protein nutrients such as meat or coagulated egg whites into their constituent amino acids (peptides). Other enzymes in the gastric juice include lipase which breaks down fats into fatty acids and glycerol. Another protein enzyme, rennin, is a component of the coagulation process in the manufacture of cheese.
Proteins that have been partially broken down by the action of pepsin may then be absorbed into the bloodstream, passed to the small intestine, and further broken down there by pancreatic enzymes. The action of gastric juice and pepsin also destroys microorganisms in the food that is being eaten.
Stomach acid is a powerful bactericidal agent and can kill bacteria in the small intestine and elsewhere in the body. Gastric acid can also damage the lining of the stomach, esophagus and throat if it refluxes back up into the esophagus, and this is often the cause of gastroesophageal reflux disease (GERD) and laryngopharyngeal reflux (LPR).
A recent study showed that the levels of pepsin in the gastric juice of patients with GERD correlate with a patient’s symptom severity and the degree of esophageal mucosal injury. Interestingly, pepsin was not found adherent to the esophageal epithelium of patients with GERD who had weak or non-acid refluxes. Instead, it was internalized by a mechanism that is not well understood and stored in intracellular vesicles with pH values below the optimal level at which pepsin is active. Whether these vesicles act as a barrier or not is unknown.
Chemical Formula of Gastric Juice and Pepsin
Pepsin is a powerful enzyme in gastric juice that digests proteins found in meat, eggs, seeds and dairy products. It is produced by glands in the mucous membrane lining of the stomach and exists in the form of an inactive zymogen called pepsinogen. Impulses from the vagus nerve and hormonal secretions, including gastrin, stimulate the release of both pepsinogen and hydrochloric acid from parietal cells within the stomach lining. The low pH caused by the HCl causes pepsinogen to unfold and then cleave itself, generating the active enzyme pepsin. Pepsin has 44 amino acids, including an extra one not present in its zymogen, which hobbles the enzyme so that it cannot digest the cell’s own proteins.
Pepsin’s digestive power is greatest under the acid conditions of normal gastric juice, but it is not fully inactivated until the pH rises to a point where the protein cutting enzymes are no longer effective. Pepsin can be retained within the cells of the lining of the stomach if the pH is low enough, but this is not good for the cells.
If the upper and lower esophageal sphincters (UES and LES) are weak, as in laryngopharyngeal reflux disease (LPR), a retrograde flow of gastric juice can enter the throat, causing irritation and damage. Pepsin is then able to digest and cleave the proteins in the pharynx, contributing to symptoms of GERD and to the pathogenesis of the disease. A study of the enzymatic activities of HGJ and duodenal juice (DJ) from 18 volunteers showed that pepsin activity did not correlate with the volume of the HGJ, but was correlated with the total proteolytic activity of the DJ, which also includes chymosin.
Chemical Structure of Gastric Juice and Pepsin
Gastric juice is a mixture of water, mucus, hydrochloric acid, and pepsin that digests proteins in the stomach lining. It is believed to destroy swallowed microorganisms, thereby preventing them from reaching the small intestine where they can cause infection. The gastric juice also contains chymotrypsin, an enzyme that breaks down peptide chains and amino acids into simple substances that can be absorbed.
Protein digestion is the primary function of the digestive system. The stomach is equipped with a unique protein-cutting enzyme called pepsin, which digests the proteins in meat or coagulated egg whites into components that can be absorbed through the intestinal wall. Pepsin is secreted in the inactive form, or zymogen, by chief cells in the stomach lining. Gastrin, vagus nerves, and the presence of food stimulate these cells to release pepsinogen and hydrochloric acid into gastric juice. Hydrochloric acid lowers the pH of gastric juice to a level that allows pepsinogen to activate.
Pepsin is composed of 44 amino acids. The zymogen is stable in neutral and alkaline environments, but when exposed to hydrochloric acid in gastric juice, the acid causes the zymogen to unfold and cleave itself autocatalytically into active pepsin. The active pepsin cuts the remaining chain of amino acids in a large active site groove until only the basic amino acid residues remain.
The acidic environment of the stomach lining is maintained by the pylorus and the lower esophageal sphincter (LES). A weak upper and lower esophageal sphincter increases the risk of a retrograde flow of gastric fluid into the larynx, which can allow pepsin to digest and damage critical structures in the throat and pharynx. In such cases, the condition is referred to as esophageal reflux disease or LPR.
Foods Acted Upon by Gastric Juice and Pepsin
The proteins in foods are acted upon by pepsin in the presence of gastric acid. The enzyme cleaves these nutrients into diffusible substances called peptones, which can be absorbed into the bloodstream. This protein digestion is an important step in the chemical digestion of foods that begins with the stomach secretions of hydrochloric acid and pepsinogen.
Glands in the mucous membrane lining of the stomach make and store pepsinogen, a precursor to the enzyme pepsin. Impulses from the vagus nerve and the hormonal secretions of gastrin and secretin stimulate the release of pepsinogen into the stomach along with the acid secreted by parietal cells. This highly acidic environment kills many microorganisms in food and also activates the enzymes that begin chemical digestion, including the proteinases pepsinogen and chymotrypsin, and the fat-digesting enzyme lipase.
Once in the stomach, hydrochloric acid combines with the zymogen pepsinogen to form the mature enzyme pepsin. Pepsin then digests the proteins in foods such as meat or coagulated egg white to their smaller peptide fragments. Gastric juice also contains the digestive enzymes gelatinase that cleaves proteins in starch-containing foods to their simple sugars and gastric lipase that digests butterfat to fatty acids and glycerol.
Pepsin is soluble in gastric acid until its pH drops below 6.5. Above this pH, it becomes denatured and irreversibly inactivated. Pepsin at pH 8.0 can be reactivated by re-acidification. This reactivation can occur in a chronically acidic reflux episode, as found in patients with gastroesophageal reflux disease and laryngopharyngeal reflux (LPR), which is associated with symptoms of hoarseness, throat pain and esophagitis.
Individual gastrointestinal juices have large variations in their enzymatic activities, pH and volume. When large pools of gastrointestinal juices are pooled together, they lose a significant portion of their activity during storage even when preservatives are added. This can lead to inaccurate results in experiments that use simulated digestion of foods.
What can inhibit the actions of gastric juice and pepsin?
The acidic gastric juice secreted in the stomach plays a vital role in the digestive process. It inactivates many swallowed microorganisms and prevents their passage to the intestines. This function has evolved to protect the stomach and esophagus from infection by pathogens. However, excessive secretion of acid may be harmful and result in reflux disease (esophageal and laryngopharyngeal).
The most important enzyme in the gastric juice is pepsin, which digests proteins from foods such as meat, eggs, seeds, dairy products, and nuts. It converts these proteins into amino acids, which are absorbed through the intestinal mucosa. Pepsin is produced in the stomach by glands in the mucous membrane lining. The glands make an inactive protein called pepsinogen, which must be cleaved or modified by other enzymes to become the active form of pepsin. Pepsinogen is activated by the H+ ions released in gastric secretions by the parietal cells.
As the pepsin moves through the stomach, it is neutralized by the hydrochloric acid in the gastric juice and its action is inhibited. This is why food must be consumed slowly and the meal well chewed.
Pepsin is also diluted by other digestive enzymes such as chyme, lipase, and proteases that are present in the gastrointestinal tract. The activity of these enzymes decreases with age. Pepsin activity is also reduced by medications that reduce the secretion of gastric acid such as proton pump inhibitors.