Introduction
This topic covers how enzyme activity is decreased by inhibitors and increased by activators. Inhibitors are classified by whether they bind reversibly or irreversibly, and for reversible inhibitors by where they bind relative to the active site. Each type changes the Michaelis constant (Km) and the maximal velocity (Vmax) in a characteristic way, which is the main thing to recognise in the exam. The topic builds on the Michaelis-Menten equation.
Reversible inhibition and its kinetics
A reversible inhibitor binds without a covalent bond, so enzyme activity returns when the inhibitor is removed or diluted. The Michaelis-Menten equation is:
Km is the substrate concentration at half Vmax, and a lower Km means higher affinity for the substrate. The three classic types of reversible inhibition differ as follows:
On a Lineweaver-Burk plot (1/v against 1/[S]), competitive inhibition gives lines that intersect on the y-axis, noncompetitive inhibition gives lines that intersect on the x-axis, and uncompetitive inhibition gives parallel lines. Mixed inhibition changes both Km and Vmax.
- Competitive examples: methotrexate inhibits dihydrofolate reductase, sulfonamides compete with PABA for dihydropteroate synthase, and statins inhibit HMG-CoA reductase. Ethanol competes with methanol and ethylene glycol at alcohol dehydrogenase, which is the basis of its use as an antidote.