zymogen
Summary
A zymogen is an inactive enzyme precursor that is activated when a protease cuts specific peptide bonds, as in trypsinogen → trypsin. Because the cleavage is covalent, activation is irreversible, and it protects the cells that make proteases from self-digestion.
Detail
Meaning: A zymogen (proenzyme) is an inactive enzyme precursor that is activated when a protease cuts specific peptide bonds, letting the protein change shape so a functional active site forms. Making proteases as zymogens protects the cells that produce them from self-digestion and allows rapid activation at the right site without new protein synthesis. Examples: trypsinogen → trypsin (by enteropeptidase), chymotrypsinogen → chymotrypsin (by trypsin), pepsinogen → pepsin (acidic pH), prothrombin → thrombin.
On the MCAT: Digestion or clotting passages ask why proteases are secreted inactive, which enzyme activates which, or what happens if trypsinogen is activated early in the pancreas (autodigestion). Trypsin activates other zymogens, so it illustrates a cascade. Zymogen activation is also classed as covalent, irreversible regulation, contrasted with reversible allosteric control, phosphorylation, and feedback inhibition.
Common confusion: A zymogen is not an enzyme blocked by a bound inhibitor. Activation cannot be reversed by removing a signal, because peptide bonds were cut. Zymogens are not limited to digestion; clotting factors and procaspases are also examples.
Sources
- Lehninger Principles of Biochemistry
- Biochemistry (Berg, Tymoczko, Stryer)
- Biochemistry (Voet and Voet)
Written for the MCAT and checked before it was published. For study reference only. Spotted an error? Let us know.