A 55-year-old man with chronic tophaceous gout is started on allopurinol. The drug works by inhibiting xanthine oxidase. Which statement about the resulting metabolic change is CORRECT?

• A Orotic acid excretion increases as a compensatory response
• B Hypoxanthine and xanthine replace uric acid and are more soluble in urine ✓
• C PRPP levels fall immediately due to increased salvage of purines
• D Serum adenosine rises, causing cardiac arrhythmias

Explanation

Allopurinol is an analog of hypoxanthine that is converted to alloxanthine (oxipurinol) by xanthine oxidase, causing suicide inhibition of the enzyme. This blocks the final steps of uric acid synthesis, causing accumulation of hypoxanthine and xanthine instead. Both are significantly more water-soluble than uric acid (solubility ~200 mg/L vs ~65 mg/L for urate at pH 7), reducing crystallization. PRPP depletion is a secondary long-term effect; orotic acid elevation occurs with UMPS deficiency.

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

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