Allopurinol lowers serum urate in gout by inhibiting xanthine oxidase. Its classification as a suicide (mechanism-based) inhibitor rests on which feature?

• A Xanthine oxidase converts it to oxypurinol, which remains tightly bound and functionally inactivates the enzyme ✓
• B It binds reversibly to the active site with a structure identical to uric acid
• C It chelates the molybdenum cofactor directly without being metabolised
• D It allosterically stabilises the inactive conformation of the enzyme

Explanation

Allopurinol is an analogue of hypoxanthine that xanthine oxidase accepts as a substrate and converts to oxypurinol (alloxanthine). Oxypurinol binds the reduced molybdenum-sulphide centre extremely tightly, effectively inactivating the enzyme, which is why the drug is called a suicide inhibitor. Option B fails because allopurinol resembles hypoxanthine, not uric acid, and option C fails because the inhibition depends on enzymatic conversion rather than direct chelation.

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

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