- Pepsin is a major digestive aspartic endopeptidase found in the gastric juice of the stomach. It is secreted as an inactive zymogen called pepsinogen by the chief cells of the gastric mucosa and is activated to pepsin in the acidic environment of the stomach (optimal pH ~1.5–2.5). This autocatalytic activation is triggered by exposure to hydrochloric acid, which is produced by the parietal cells.
- Pepsin catalyzes the hydrolysis of internal peptide bonds (endopeptidase activity), preferentially cleaving adjacent to aromatic (e.g., phenylalanine, tryptophan, tyrosine) and hydrophobic amino acids. Unlike serine or metalloproteases, pepsin utilizes two aspartate residues in its active site to activate a water molecule for nucleophilic attack on the peptide bond. This mechanism is characteristic of the aspartic protease family, to which pepsin belongs.
- Functionally, pepsin initiates protein digestion in the stomach, breaking large protein molecules into smaller peptides. These peptides are further digested by pancreatic enzymes in the small intestine. Pepsin is particularly effective at digesting collagen and other tough proteins, aiding in the breakdown of meat and other dense food components.
- Due to its acid-stable nature, pepsin is widely used in industrial and laboratory applications, including the preparation of protein hydrolysates, digestion of antibodies to produce Fab fragments, and analysis of protein structure through limited proteolysis. It is also employed in diagnostic tools to assess gastric function or detect pepsin presence in respiratory samples as a marker for gastric reflux.
- In summary, pepsin is a crucial digestive enzyme and the prototypical aspartic protease. It operates efficiently under acidic conditions and plays a vital role in initiating protein breakdown in the human gastrointestinal tract.
