Enzyme Inhibition Types: Competitive, Uncompetitive, Noncompetitive & Reversible

Irreversible inhibition

Inhibitor covalently modifies the enzyme, disrupting the binding site and eliminating enzyme activity.

Reversible inhibition

Inhibition in which the inhibitor binds reversibly to the enzyme.

Competitive inhibitor

Binds reversibly to the active site of enzymes.

Competitive inhibition: complex formed

Forms a nonproductive enzyme-inhibitor complex (EI).

Competitive inhibition: substrate relationship

Substrate and inhibitor compete for binding to the active site.

Competitive inhibition: KM

Increases KM because more [S] is needed to reach ½ Vmax.

Competitive inhibition: Vmax

No effect on Vmax.

Uncompetitive inhibitor

Binds reversibly to the enzyme-substrate complex.

Uncompetitive inhibition: complex formed

Forms a nonproductive enzyme-inhibitor complex (ESI).

Uncompetitive inhibition: KM and Vmax

Affects both KM and Vmax.

Noncompetitive inhibitor

Binds reversibly outside the active site of enzymes.

Noncompetitive inhibition: complex formed

Forms a nonproductive EI or ESI complex.

Noncompetitive inhibition: substrate relationship

Substrate and inhibitor bind independently to the enzyme.

Noncompetitive inhibition: Vmax

Lowers Vmax.

Noncompetitive inhibition: KM

No effect on KM.

Methotrexate

Competitive inhibitor of dihydrofolate reductase used as an anticancer drug.

Transition-state analog inhibitor

Competitive inhibitors can be modeled after the transition state because enzymes often have a higher affinity for the transition state.