In enzyme kinetics, a competitive inhibitor increases the apparent Km without changing Vmax, while an uncompetitive inhibitor DECREASES both Km and Vmax. Which type of inhibition is characteristic of aspirin's irreversible inhibition of cyclooxygenase (COX)?

• A Irreversible covalent (suicide) inhibition ✓
• B Reversible competitive inhibition
• C Non-competitive inhibition
• D Uncompetitive inhibition

Explanation

Aspirin (acetylsalicylic acid) irreversibly acetylates the active-site serine residue (Ser-529 in COX-1, Ser-516 in COX-2) via covalent modification, permanently inactivating the enzyme — a mechanism-based or suicide inhibition. COX cannot be reactivated; new enzyme protein must be synthesized. This is why aspirin's antiplatelet effect lasts the lifespan of the platelet (~7-10 days), as anucleate platelets cannot synthesize new COX. True competitive, non-competitive, and uncompetitive inhibitions are all reversible.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

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