In the purine salvage pathway, hypoxanthine-guanine phosphoribosyltransferase (HGPRT) catalyses the conversion of hypoxanthine + PRPP to IMP and guanine + PRPP to GMP. In Lesch-Nyhan syndrome (complete HGPRT deficiency), what biochemical consequence directly elevates uric acid?

• A Decreased PRPP availability reduces de novo purine synthesis
• B Defective HGPRT directly catalyses uric acid synthesis
• C Increased PRPP levels suppress PRPP amidotransferase
• D Accumulated hypoxanthine and guanine are oxidised to uric acid by xanthine oxidase ✓

Explanation

When HGPRT is absent, hypoxanthine and guanine cannot be salvaged back to IMP and GMP respectively. Instead, both are degraded: hypoxanthine is oxidised by xanthine oxidase to xanthine, then to uric acid; guanine is deaminated to xanthine and then oxidised to uric acid. Additionally, PRPP that would have been used in salvage accumulates, driving increased de novo purine synthesis and further uric acid production. This causes severe hyperuricaemia, nephropathy, and the characteristic neurological features (self-mutilation, choreoathetosis). HGPRT itself does not synthesise uric acid.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.