Pepsin

Pepsin is a proteolytic enzyme that digests proteins in the stomach. It is an endopeptidase that cleaves peptide bonds within proteins, with a preference for hydrophobic residues at the cleavage site. It is active in the highly acidic environment of the stomach, with an optimal pH around 1.5 to 2.5. Pepsin works in concert with hydrochloric acid produced by parietal cells to initiate protein digestion.

Pepsin is secreted by chief cells as an inactive zymogen, pepsinogen. The acidic gastric lumen cleaves a peptide fragment to form active pepsin; activation can be autocatalytic, and occurs efficiently at low pH.

Pepsin belongs to the aspartic protease family; its active site contains two aspartate residues that activate a water molecule to attack the peptide bond. It shows broad specificity, often cleaving bonds near hydrophobic amino acids such as phenylalanine, leucine, methionine, and tryptophan.

In humans, pepsin facilitates the initial digestion of dietary proteins in the stomach; most protein digestion occurs later in the small intestine by pancreatic enzymes. Pepsin originates from gastric mucosa and is conserved in many mammals and other vertebrates.

Pepsin can be inhibited by pepstatin, a specific inhibitor of aspartic proteases. Measurement of pepsin or pepsinogen levels in gastric secretions or blood is used in research on gastric function and certain gastrointestinal disorders.