zymogeny

Zymogeny is the process by which inactive enzyme precursors, known as zymogens or proenzymes, are converted into their active forms. Inactive zymogens typically contain an inhibitory propeptide that blocks the catalytic site. Activation usually involves proteolytic cleavage or conformational changes that remove or reorganize the inhibitory segment, enabling enzymatic activity. Storing enzymes as zymogens helps prevent unintended proteolysis of cellular components and allows controlled activation in specific contexts.

Many digestive enzymes are secreted as zymogens. Pepsin is produced as pepsinogen in the stomach and activated by gastric acid. The pancreas secretes several zymogens, including trypsinogen and chymotrypsinogen; in the small intestine, enteropeptidase activates trypsinogen to trypsin, and trypsin then activates other pancreatic zymogens in a proteolytic cascade. Other examples include proelastase and procarboxypeptidases, which are activated downstream to digest various proteins and peptides.

Zymogen activation is a key feature of several physiological cascades beyond digestion. In blood coagulation and certain immune pathways, a series of zymogens are sequentially activated to amplify responses and coordinate rapid proteolysis. The regulated nature of these cascades helps ensure responses occur at the right time and place.

Clinical relevance arises when zymogen activation is defective or occurs inappropriately. Premature activation of pancreatic trypsinogen within the pancreas can lead to pancreatitis, while mutations affecting zymogen function can contribute to coagulation disorders or other proteolytic diseases. Understanding zymogen regulation provides insight into normal physiology and disease mechanisms.

Etymology: the term derives from Greek zymē, meaning ferment or leaven, and genēs, producing.