Allopurinol is used to treat gout. Beyond inhibiting xanthine oxidase, which additional biochemical effect contributes to its urate-lowering action?
- A Oxypurinol (its active metabolite) is converted by HGPRT to oxypurinol ribotide, which inhibits PRPP amidotransferase ✓
- B It directly inhibits PRPP synthetase, reducing de novo purine synthesis
- C It activates HGPRT, channelling purines into the salvage pathway
- D It induces uricosuric renal tubular secretion of urate
Correct answer: A. Oxypurinol (its active metabolite) is converted by HGPRT to oxypurinol ribotide, which inhibits PRPP amidotransferase
Explanation
Allopurinol is oxidised by xanthine oxidase to oxypurinol (alloxanthine), which is a tight-binding irreversible inhibitor of xanthine oxidase. Additionally, oxypurinol is phosphoribosylated by HGPRT to form oxypurinol-7-ribotide, which inhibits PRPP amidotransferase — the first committed step of de novo purine synthesis — thereby reducing purine biosynthesis upstream. This dual mechanism is more effective than xanthine oxidase inhibition alone.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
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