A zymogen (or proenzyme) is an inactive enzyme precursor. A zymogen requires a biochemical change (such as a hydrolysis reaction revealing the active site, or changing the configuration to reveal the active site) for it to become an active enzyme. The biochemical change usually occurs in a lysosome where a specific part of the precursor enzyme is cleaved in order to activate it. The inactivating piece which is cleaved off can be a peptide unit, or can be independently folding domains comprising more than 100 residues. Although they limit the enzyme's ability, these n-terminal extensions of the enzyme or a “prosegment” often aid in the stabilizing and folding of the enzyme they inhibit.
The pancreas secretes zymogens partly to prevent the enzymes from digesting proteins in the cells in which they are synthesised. Enzymes like pepsin are created in the form of pepsinogen, an inactive zymogen. Pepsinogen is activated when chief cells release it into HCl which partially activates it. Another partially activated pepsinogen completes the activation by removing the peptide turning the pepsinogen into pepsin. Accidental activation of zymogens can happen when the secretion duct in the pancreas is blocked by a gallstone resulting in acute pancreatitis.
Fungi also secrete digestive enzymes into the environment as zymogens. The external environment has a different pH than inside the fungal cell and this changes the zymogen's structure into an active enzyme.
Examples of zymogens:
- Most proteins in the coagulation system
- Some of the proteins of the complement system
- Webster entry on zymogen
- www.proteinscience.org:Molecular mechanisms for the conversion of zymogens to active proteolytic enzymes