unkompetitiven

Unkompetitiv, or uncompetitive inhibition, is a mode of enzyme inhibition in biochemistry in which an inhibitor binds exclusively to the enzyme–substrate complex (ES) rather than to the free enzyme. Binding to ES forms an enzyme–substrate–inhibitor complex (ESI) that impedes catalysis and reduces the turnover rate.

Kinetics and mechanism: The inhibitor binds with a dissociation constant for the ES complex. In the presence of the inhibitor, both the apparent Km and Vmax are reduced: Km,app = Km / (1 + [I]/Ki'), Vmax,app = Vmax / (1 + [I]/Ki'). Consequently, the ratio Km,app/Vmax,app equals Km/Vmax, so the Lineweaver–Burk plot shows parallel lines, all with the same slope Km/Vmax but different intercepts.

Substrate dependence: Because the inhibitor targets ES, its effect increases with substrate concentration; higher substrate promotes formation of ES and thus more target for the inhibitor. Therefore uncompetitive inhibition cannot be fully overcome by increasing substrate, unlike competitive inhibition.

Occurrence and study: Uncompetitive inhibition is less common than competitive or noncompetitive modes and is often observed in specific enzyme–inhibitor systems under particular conditions. It is identified experimentally by kinetics that show parallel double-reciprocal plots and by measurements showing decreases in both Km and Vmax.

Relation to other inhibition types: It differs from competitive inhibition (binding to the free enzyme active site) and noncompetitive inhibition (inhibitor binds enzyme with or without substrate, typically affecting Vmax but not Km). Uncompetitive inhibition is most effective at high substrate levels and has distinct implications for drug design and metabolic regulation.