proenzymy

A proenzyme, also called a zymogen, is an inactive precursor of an enzyme that becomes active only after a specific biochemical change, typically proteolytic cleavage. Proenzymes allow cells to synthesize potentially hazardous enzymes in a controlled form, preventing autodigestion and damage to tissues. Activation usually occurs in a defined location or context and is often part of a proteolytic cascade; the cleavage removes regulatory segments or induces a conformational change that reveals the enzyme’s active site.

In physiology, many proenzymes are involved in digestion. Examples include pepsinogen, which is converted to pepsin in the stomach’s acidic environment; and trypsinogen, which is activated to trypsin by the intestinal enzyme enteropeptidase in the small intestine. Other pancreatic zymogens include chymotrypsinogen, proelastase, and procarboxypeptidases, all of which become active proteases during digestion.

Proenzymes also play critical roles in coagulation and immunity. In the blood coagulation cascade, several zymogens (such as prothrombin) circulate in inactive form and are activated in a regulated sequence to produce thrombin, which then cleaves fibrinogen to form clots. Additional systems, including the complement pathway, deploy zymogens that are activated to proteases in response to immune challenges.

Clinical relevance and regulation: Tight control of zymogen activation is essential to prevent tissue damage; premature or inappropriate activation can lead to conditions such as pancreatitis or bleeding disorders. Therapeutic interventions often target steps in zymogen activation cascades, illustrating the medical significance of proenzymes.

Terminology note: the terms proenzyme and zymogen are often used interchangeably, though “proenzyme” is a broader term that can include non-enzymatic precursor concepts; for example, proinsulin is a precursor of insulin but not a zymogen.