Pepsin is the most important digestive enzyme of the stomach. With its help, food proteins are broken down into so-called peptones. Pepsin is active only in a very acidic environment and, together with stomach acid, can attack the stomach lining in the event of illness.
What is pepsin?
Pepsin represents a gastric enzyme that already predigests the dietary proteins of the food pulp. These are broken down by pepsin in the acidic environment of the stomach to form the so-called peptones. The enzyme is only active in an acidic environment at a pH of 1.5 to 3. Above a pH of 6, pepsin is irreversibly inactivated. The enzyme is also added to certain foods to promote digestion. The famous pepsin wine or Pepsi Cola also contain this enzyme. Pepsin was discovered as early as 1836 by the German physiologist Theodor Schwann. It was not until 1930 that the American chemist John Howard Northrop was able to present it in crystalline form. Pepsin is formed from the inactive form pepsinogen by the action of gastric acid. No enzyme is required for this reaction. It is an autoproteolysis. With cleavage of 44 amino acids, the active pepsin is formed, which consists of 327 amino acids and is a phosphoprotein.
Function, action, and tasks
Pepsin has the task of predigesting the proteins of the food pulp already in the stomach. This involves cleavage of the individual proteins into polypeptide chains known as peptones. Pepsin is a so-called endopeptidase. In contrast to exopeptidases, an endopeptidase cleaves protein molecules inside the polypeptide chain. In most cases, cleavage takes place at specific amino acids. In pepsin, the chain is cleaved at aromatic amino acids. Mainly the cleavage takes place after the amino acid phenylalanine. Responsible for the specific action of the enzyme are two aspartates (aspartic acid) in the functional center. The resulting peptones are already so short that they can no longer be called proteins. They have also lost the ability to form secondary, tertiary or quaternary structures. This means that coagulation no longer occurs and the polypeptide chains remain water-soluble when they pass into the duodenum. In the small intestine, they can then be easily further degraded to amino acids by proteases from the pancreas. The precursor of pepsin, as mentioned earlier, is the inactive pepsinogen. Pepsinogen is synthesized in the stomach cells and must initially remain inactive so as not to attack the body’s own proteins. It is only through the action of hydrochloric acid in the stomach that pepsin is formed. However, the stomach protects itself from self-digestion of the gastric mucosa by pepsin by forming an alkaline mucus. Via gastric peristalsis, the food pulp is circulated several times, and only the proteins are transformed into peptones. Fats and carbohydrates spared from predigestion by saliva pass through the stomach unchanged until they reach the small intestine. Only then are these food components also broken down further by the digestive secretions of the pancreas. In addition to the food pulp, bacteria are also killed in the acidic environment of the stomach and their proteins are broken down by pepsin. However, there is one bacterium that survives even these extreme conditions and can continue to exist in the stomach. This is Helicobacter pylori. When the bacteria leave the stomach, the more alkaline enzymes of the pancreas gain influence. In the process, the enzyme pepsin is irreversibly inactivated by the high pH and can now also be degraded by the proteases of the pancreas.
Formation, occurrence, properties, and optimal values
All animals with a stomach-like digestive organ produce pepsin to predigest dietary proteins. The enzyme can be obtained from the stomachs of animals. It is added to certain foods to aid digestion. Pepsin wine and Pepsi Cola also contain pepsin. Pepsin can only exert its effect together with gastric acid. An acidic environment is necessary for its function. Production of the pepsin precursor pepsinogen is stimulated by the hormone gastrin. In turn, gastrin production is stimulated by distension of the stomach, by proteins in the food pulp, and by alcohol or caffeine.
Diseases and disorders
Despite their aggressiveness, gastric acid and pepsin cannot attack the gastric mucosa.However, if the stomach is colonized with the bacterium Helicobacter pylori, chronic gastritis or even gastric or duodenal ulcers can occur. To protect the gastric mucosa, the gastric vesicle cells form an alkaline mucus that protects the gastric mucosa. However, Helicobacter pylori breaks down the protective mucus layer, so that the hydrochloric acid of the stomach and the enzyme pepsin can attack the gastric mucosa directly. This leads to constant accumulation of the mucous membrane with the formation of chronic inflammation or even an ulcer. In the long term, chronic ulcers and inflammation can also lead to stomach cancer. The disease is manifested by frequent and severe heartburn, burning stomach pain and even vomiting. At times, vomiting of blood also occurs. Treatment consists in combating Helicobacter pylori by antibiotic administration. However, not all diseases of the stomach with destruction of the gastric mucosa are due to the bacterium. Increased acidity and pepsin formation can also be caused by functional processes. If these processes disturb the balance between the secretions protecting the mucosa and gastric acid, reflux disease may also result. Hormonal processes can also lead to this. For example, in Zollinger-Ellison syndrome, a neuroendocrine tumor in the pancreas called a gastrinoma constantly produces too much gastrin and thus too much gastric acid as well as pepsin.
