Irreversible inhibition of enzymes differs fundamentally from reversible inhibition. Aspirin (acetylsalicylic acid) irreversibly inhibits COX by:

• A Chelating the haem iron at the COX active site
• B Forming a covalent bond with the catalytic His residue via aspirin's acetyl group
• C Competitively displacing arachidonate with a very high-affinity interaction (Kd < 1 nM)
• D Acetylating Serine-530 of COX-1 and Serine-516 of COX-2, permanently blocking the arachidonic acid channel ✓

Explanation

Aspirin's acetyl group is transferred to the hydroxyl of a specific serine residue (Ser-530 in COX-1, Ser-516 in COX-2) that lies in the substrate channel, permanently blocking arachidonic acid access. Because platelets lack nuclei and cannot synthesise new COX protein, this irreversible inhibition persists for the platelet's entire lifespan (~10 days). Low-dose aspirin selectively inhibits platelet COX-1 (TXA2 synthesis) more than vascular endothelial COX-2 (PGI2 synthesis), conferring net antithrombotic effect.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.