Allopurinol treats gout by inhibiting xanthine oxidase. Which ADDITIONAL biochemical effect of allopurinol reduces de novo purine synthesis?
- A Allopurinol ribonucleotide accumulation inhibits PRPP amidotransferase, the rate-limiting step of de novo purine synthesis ✓
- B Allopurinol directly inhibits phosphoribosylpyrophosphate (PRPP) synthetase
- C Xanthine oxidase inhibition lowers IMP availability, reducing salvage pathway flux
- D Allopurinol activates HGPRT, diverting purines to salvage and away from degradation
Correct answer: A. Allopurinol ribonucleotide accumulation inhibits PRPP amidotransferase, the rate-limiting step of de novo purine synthesis
Explanation
Allopurinol, a structural analogue of hypoxanthine, is converted by xanthine oxidase to oxipurinol (alloxanthine). Additionally, HGPRT converts allopurinol to allopurinol ribonucleotide (allopurinol-5'-monophosphate), which inhibits PRPP amidotransferase — the committed, rate-limiting step of de novo purine synthesis. This dual mechanism reduces both uric acid production and de novo purine overproduction.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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