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Biochemistry · Enzyme inhibition: irreversible inhibition by aspirin
Sample itemA man takes aspirin 75 mg daily. A bleeding time measured three days after he stops aspirin is still prolonged, although aspirin has a plasma half-life of only about 20 minutes. Which statement best explains this?
Original practice item, not a recalled exam question. Nothing here is recorded.
The answer and the reasoning
D. Aspirin irreversibly acetylates a serine of cyclooxygenase-1, and anucleate platelets cannot make new enzyme
Aspirin is a covalent, irreversible inhibitor: it transfers an acetyl group to a serine near the active site of COX-1, blocking arachidonate access and thromboxane A2 synthesis. Platelets have no nucleus, so they cannot make fresh enzyme and the block lasts for the 7 to 10 day platelet life span. Function returns only as new platelets enter the circulation.
Option by option
A. Aspirin binds the cyclooxygenase active site reversibly but dissociates from it very slowly
Slow dissociation would still allow recovery within hours or days of plasma clearance; the block here is covalent.
B. Aspirin damages megakaryocyte DNA so that newly formed platelets lack thromboxane synthase
Aspirin does not damage megakaryocyte DNA, and new platelets released later have normal COX-1.
C. Aspirin is stored in platelet granules and is released from them slowly over several days
Aspirin is not stored in granules; its action depends on covalent modification of cyclooxygenase in the platelet.
D. Aspirin irreversibly acetylates a serine of cyclooxygenase-1, and anucleate platelets cannot make new enzyme (correct)
Covalent acetylation of serine in COX-1 cannot be reversed in an anucleate platelet, so the effect outlasts the drug.
Source note: Original NextPrep sample item — pending expert review. This item is original practice material awaiting independent expert review, so confirm important facts in a standard textbook.
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