trypsinogen

Trypsinogen is produced by pancreatic acinar cells and stored in zymogen granules, then secreted into the pancreatic duct in its inactive form to prevent autodigestion of the pancreas. Upon reaching the duodenum, brush border enzyme enteropeptidase (enterokinase) cleaves trypsinogen to produce active trypsin. Trypsin then autocatalytically activates more trypsinogen and also activates other pancreatic zymogens (chymotrypsinogen, proelastase, procarboxypeptidase, prophospholipase A2) into their active forms, amplifying protein digestion in the small intestine. Trypsin cleaves peptide bonds on the carboxyl side of lysine and arginine residues. Clinically, premature intra-pancreatic activation of trypsinogen (due to gene mutations such as PRSS1, SPINK1, or CFTR mutations, gallstones, alcohol, or hypertriglyceridemia) leads to autodigestion of pancreatic tissue and is a key mechanism in acute and hereditary pancreatitis. Normally, the pancreas protects itself via trypsin inhibitors (e.g., SPINK1/pancreatic secretory trypsin inhibitor) that inactivate any prematurely activated trypsin. Fecal elastase and trypsinogen levels can be used clinically to assess pancreatic exocrine function (e.g., low levels in chronic pancreatitis or cystic fibrosis). Elevated serum trypsinogen (immunoreactive trypsinogen) is used in newborn screening for cystic fibrosis.