Zymogene

A zymogen, also called a proenzyme, is an inactive precursor of an enzyme that requires proteolytic cleavage to become catalytically active. Zymogens are typically synthesized in secretory cells and stored in vesicles, where they remain inactive until they reach their site of action.

Activation generally occurs through proteolytic processing that removes a small peptide segment known as the propeptide. This cleavage induces structural changes that expose the active site and render the enzyme functional. In many biological systems, zymogens are part of regulated cascades in which one activated enzyme activates others, amplifying the response while keeping activity largely compartmentalized to prevent damage to the producing cells.

Common examples of zymogens include pancreatic digestive enzymes such as trypsinogen, chymotrypsinogen, procarboxypeptidases, and proelastase. These pancreatic zymogens are secreted into the small intestine, where proteases like enterokinase (enteropeptidase) convert trypsinogen to trypsin, and trypsin in turn activates the other zymogens, creating an enzymatic cascade for protein digestion.

Zymogens also appear in other physiological pathways, including blood coagulation, where precursor proteases are activated in a regulated sequence to form active coagulation factors.

Clinical relevance includes prevention of autodigestion in secretory tissues and the consequences of dysregulated activation. Premature activation of pancreatic zymogens within the pancreas can lead to pancreatitis, and genetic changes affecting zymogen activation or inhibition (for example in PRSS1 or SPINK1) influence disease risk. Defects in zymogen formation or activation can impair normal digestive or physiological processes.