Clavulanic acid is a mechanism-based ('suicide') β-lactamase inhibitor. What distinguishes mechanism-based inhibitors from competitive inhibitors in terms of enzyme kinetics?

• A Mechanism-based inhibitors increase Km without changing Vmax; competitive inhibitors reduce Vmax
• B Mechanism-based inhibitors are processed by the target enzyme, forming a covalent adduct that irreversibly inactivates it; competitive inhibitors bind reversibly to the active site ✓
• C Mechanism-based inhibitors are prodrugs activated by non-enzymatic hydrolysis; competitive inhibitors are active drugs
• D Mechanism-based inhibitors act at allosteric sites; competitive inhibitors act at the substrate-binding active site

Explanation

Mechanism-based (or 'suicide') inhibitors are substrates that are initially processed by the enzyme through normal catalytic steps, generating a reactive intermediate that irreversibly covalently modifies and inactivates the enzyme. Clavulanic acid is recognised by β-lactamase, its β-lactam ring is cleaved in the normal way, but the resulting acylenzyme intermediate undergoes rearrangement to form a stable covalent adduct — the enzyme has committed 'suicide'. This is irreversible, unlike competitive inhibitors which are reversible and increase Km. Examples include clavulanate, sulbactam, tazobactam (class A β-lactamase inhibitors) and newer non-β-lactam inhibitors like avibactam.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.