Biochemistry · Amino Acid Metabolism and Urea Cycle (Disorders, Phenylketonuria)

Allopurinol is used to treat gout. Its mechanism of action involves which biochemical step in purine catabolism?

  • A Inhibits xanthine oxidase, reducing conversion of hypoxanthine/xanthine to uric acid
  • B Inhibits adenosine deaminase, reducing inosine formation
  • C Activates HGPRT salvage pathway to reutilize purines
  • D Inhibits PRPP synthetase, reducing de novo purine synthesis initiation
Correct answer: A. Inhibits xanthine oxidase, reducing conversion of hypoxanthine/xanthine to uric acid

Explanation

Allopurinol is a structural analogue of hypoxanthine that competitively inhibits xanthine oxidase. It is also converted to oxipurinol (alloxanthine) by xanthine oxidase, which then forms a tight covalent complex with the reduced molybdenum cofactor of xanthine oxidase causing mechanism-based irreversible inhibition. This blocks conversion of hypoxanthine → xanthine → uric acid. Hypoxanthine and xanthine accumulate but are more soluble than uric acid. Allopurinol also reduces PRPP availability indirectly (by increased salvage of hypoxanthine via HGPRT, consuming PRPP) but this is secondary, not its direct mechanism. It does not directly activate HGPRT or inhibit ADA.

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

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