trypsin

Trypsin is synthesized in pancreatic acinar cells as the zymogen trypsinogen, stored in zymogen granules, and secreted into the duodenum via the pancreatic duct. Enteropeptidase (enterokinase), located on the duodenal brush border, cleaves trypsinogen to form active trypsin. Trypsin then autocatalytically activates more trypsinogen and also activates other pancreatic proenzymes—chymotrypsinogen to chymotrypsin, proelastase to elastase, and procarboxypeptidase to carboxypeptidase—making it the master activator of the pancreatic digestive enzyme cascade.

Mechanistically, trypsin is a serine protease with a catalytic triad (His57, Asp102, Ser195) that hydrolyzes peptide bonds specifically after lysine or arginine residues, contributing to the breakdown of dietary proteins into oligopeptides and amino acids for absorption.

Clinical significance: Premature activation of trypsinogen within the pancreas (due to gene mutations, gallstones, alcohol, or other insults) leads to autodigestion of pancreatic tissue and acute pancreatitis. PRSS1 gene mutations cause hereditary pancreatitis by making trypsinogen resistant to inactivation or more easily autoactivated. SPINK1 mutations (a trypsin inhibitor) and CFTR mutations are also associated with chronic pancreatitis due to impaired protection against premature trypsin activation. Trypsin activity is measured indirectly in some pancreatic function tests. Fecal elastase and trypsin levels can be used to assess exocrine pancreatic insufficiency (e.g., in cystic fibrosis). In laboratory and clinical settings, trypsin is also used to detach adherent cells in tissue culture and is a component in some digestive enzyme replacement therapies for pancreatic insufficiency.