zimogens

Zymogens, also known as proenzymes, are inactive precursor enzymes that require a biochemical change to become active. Most commonly this change is proteolytic cleavage of a short peptide segment that destabilizes an inhibitory region and exposes the active site. Zymogens are typically synthesized in secretory cells and stored in secretory granules or vesicles to prevent unintended proteolysis.

The best-known examples are digestive zymogens. Pepsinogen, secreted by gastric chief cells, is activated to pepsin in the acidic environment of the stomach. The pancreas secretes trypsinogen, chymotrypsinogen, proelastase, and procarboxypeptidases A and B. In the duodenum, enteropeptidase converts trypsinogen to trypsin, which then activates the other pancreatic zymogens in a proteolytic cascade. Zymogens also play roles outside digestion, such as plasminogen (to plasmin) in fibrinolysis and prothrombin (to thrombin) in coagulation. Activation is tightly regulated and spatially restricted to prevent damage to the tissues that synthesize them.

Clinical and physiological significance arise from the need to control proteolysis. Premature activation of pancreatic zymogens can lead to pancreatitis, a condition associated with digestive tissue autodigestion. Genetic mutations affecting zymogen activation or regulation (for example, trypsinogen mutations) can predispose to hereditary pancreatitis. Proper zymogen regulation is essential for normal digestion and maintenance of tissue integrity.