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Biochemistry · Nucleotide metabolism: effect of allopurinol on purine excretion
Sample itemA patient with gout is started on allopurinol. Serum uric acid falls, and a later urine analysis shows increased hypoxanthine and xanthine excretion. What explains the changed excretion pattern?
Original practice item, not a recalled exam question. Nothing here is recorded.
The answer and the reasoning
C. Blocked oxidation of hypoxanthine and xanthine to uric acid
Allopurinol and its metabolite oxypurinol inhibit xanthine oxidase, so hypoxanthine and xanthine accumulate and are excreted instead of uric acid. These oxypurines are more soluble than urate, so crystal deposition falls. Some hypoxanthine is salvaged, which also reduces de novo synthesis.
Option by option
A. Increased activity of the salvage pathway enzyme HGPRT
Salvage activity is not the cause, and HGPRT is not increased by this drug.
B. Failure of PRPP synthesis
PRPP synthesis is not inhibited by allopurinol, and less PRPP would not explain oxypurine excretion.
C. Blocked oxidation of hypoxanthine and xanthine to uric acid (correct)
Correct. Inhibiting xanthine oxidase shifts excretion to the more soluble oxypurine precursors.
D. Increased degradation of uric acid to allantoin
Humans lack uricase, so uric acid is not degraded to allantoin by allopurinol.
Source note: Original NextPrep sample item — pending expert review. This item is original practice material awaiting independent expert review, so confirm important facts in a standard textbook.
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