Allopurinol is used to lower uric acid in chronic tophaceous gout. Its active metabolite oxipurinol inhibits xanthine oxidase. As a result of enzyme inhibition, the immediate biochemical effect on xanthine and hypoxanthine levels is:

• A Xanthine and hypoxanthine decrease as substrate is diverted to the salvage pathway
• B Xanthine and hypoxanthine accumulate as substrate cannot be oxidised to uric acid ✓
• C Allopurinol directly degrades uric acid to allantoin, normalising xanthine levels
• D Xanthine is converted to uric acid via an alternative aldehyde oxidase pathway

Explanation

Xanthine oxidase sequentially oxidises hypoxanthine → xanthine → uric acid. Oxipurinol (active metabolite of allopurinol) is a suicide inhibitor that covalently modifies the molybdenum cofactor of xanthine oxidase. With enzyme inhibition, hypoxanthine and xanthine accumulate and are excreted in urine instead of uric acid; their combined solubility in urine is greater than uric acid, reducing stone risk. Uric acid falls. Allopurinol does not directly catabolise uric acid; that pathway (via uricase) exists in other species but not humans. Aldehyde oxidase can oxidise allopurinol to oxipurinol but does not efficiently catabolise xanthine.

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

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