Which enzyme is inhibited by allopurinol in the treatment of gout?

• A. Uricase
• B. Hypoxanthine-guanine phosphoribosyl transferase
• C. Xanthine oxidase
• D. Hypoxanthine reductase

Answer: (C)

Allopurinol works by blocking the enzyme that generates uric acid from purines. It is a structural analog of hypoxanthine and is processed by xanthine oxidase; during this process, oxypurinol forms and then potently inhibits xanthine oxidase. With XO inhibited, the conversion of hypoxanthine to xanthine and of xanthine to uric acid slows down, leading to lower uric acid production and relief from gout symptoms. Uricase, which some organisms use to oxidize uric acid to a more soluble compound, is not a target in humans and is not inhibited by allopurinol. HGPRT is a salvage enzyme in purine metabolism and is not inhibited by allopurinol; inhibiting it would not reduce uric acid. Hypoxanthine reductase is not a relevant enzyme in this context. Therefore, the enzyme inhibited by allopurinol is xanthine oxidase.