pepsinogeen

Pepsinogen is the zymogen (inactive precursor) form of the digestive enzyme pepsin. It is an inactive proenzyme produced mainly by the chief cells of the gastric mucosa and secreted into the stomach lumen as part of gastric juice. The inactive form helps protect the stomach’s glandular tissue from autodigestion by acid, and it is stored in zymogen granules for release with meals. In humans, pepsinogen is encoded by two gene families, PGA and PGB, which give rise to the two major forms, pepsinogen I and pepsinogen II. Pepsinogen I is predominantly produced by the fundic glands of the body of the stomach, whereas pepsinogen II is secreted by both fundic and pyloric glands; these forms differ in distribution and concentration along the stomach.

Pepsinogen is activated to the proteolytic enzyme pepsin under acidic conditions. In the highly acidic environment of the stomach (pH around 1 to 3), pepsinogen undergoes autocatalytic cleavage that removes an N-terminal activation peptide, yielding pepsin. Pepsin can also activate additional pepsinogen molecules, amplifying digestion. Pepsin is an aspartic protease with optimal activity at very low pH, and it initiates the digestion of proteins by cleaving peptide bonds, with a preference for hydrophobic and aromatic residues. Its activity declines sharply as pH rises above about 4.

Clinically, measurements of pepsinogen levels in serum or plasma, especially the ratios of pepsinogen I to II, are used as noninvasive markers of gastric mucosal status. Low pepsinogen I or a low pepsinogen I/II ratio can indicate atrophic gastritis, a condition associated with increased risk for gastric cancer. Pepsinogen levels can also reflect changes in gastric function with age, medications, or disease.