A patient with gout is started on allopurinol. The drug inhibits xanthine oxidase. Which intermediate accumulates in the blood and why does it cause fewer problems than uric acid?

• A Adenosine — more freely filtered and non-crystallizing
• B Hypoxanthine and xanthine — more soluble than uric acid at physiologic pH ✓
• C Orotic acid — metabolized by OPRT to UMP rapidly
• D GMP — reincorporated into nucleotide pool via salvage

Explanation

Allopurinol (and its active metabolite oxypurinol) inhibits xanthine oxidase, reducing conversion of hypoxanthine → xanthine and xanthine → uric acid. Hypoxanthine and xanthine accumulate but are significantly more soluble in urine at physiological pH than uric acid (uric acid pKa ~5.8, so it is minimally ionized and poorly soluble at acidic urine pH). Xanthine is slightly less soluble than hypoxanthine but still far more soluble than uric acid, so precipitation and tophi formation is prevented. Rarely, xanthine nephropathy can occur with high-dose allopurinol.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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