Allopurinol is used to treat gout and to prevent tumour lysis syndrome during chemotherapy. Allopurinol is a prodrug — it undergoes conversion by xanthine oxidase to alloxanthine (oxypurinol), which then inhibits xanthine oxidase. This pattern of inhibition (where the substrate is converted to an inhibitor by the target enzyme) is called:

• A Non-competitive inhibition
• B Transition state analogue inhibition
• C Product inhibition
• D Mechanism-based (suicide) inhibition ✓

Explanation

Mechanism-based inhibition (suicide inhibition) occurs when an enzyme converts a substrate-like molecule into an inhibitor that then irreversibly (or very tightly) inhibits the same enzyme. Allopurinol (a hypoxanthine analogue) is oxidised by xanthine oxidase to alloxanthine (oxypurinol), which tightly binds the reduced molybdenum cofactor (MoCo) at the active site in a covalent-like fashion, producing long-lasting inhibition. This makes allopurinol a prodrug requiring xanthine oxidase for activation. Key drug interaction: azathioprine and 6-mercaptopurine are also inactivated by xanthine oxidase, so their doses must be reduced by 75% when co-administered with allopurinol to prevent life-threatening myelotoxicity.

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

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Written and medically reviewed by the StethoPrep medical team.