A 3-year-old boy presents with self-mutilating behaviour, hyperuricemia and neurological deficits. The enzyme deficient in Lesch-Nyhan syndrome is HGPRT, which catalyses which reaction?

• A IMP → XMP using NAD+
• B Hypoxanthine + PRPP → IMP + PPi (and guanine + PRPP → GMP + PPi) ✓
• C Hypoxanthine → xanthine by xanthine oxidase
• D AICAR → inosine in de novo purine synthesis

Explanation

Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) catalyses the salvage of hypoxanthine and guanine: hypoxanthine + PRPP → IMP + PPi and guanine + PRPP → GMP + PPi. Deficiency of HGPRT abolishes purine salvage, causing hypoxanthine and guanine accumulation, which are oxidised by xanthine oxidase to uric acid (hyperuricemia, gout, urate nephropathy). The neurological symptoms (choreoathetosis, self-mutilation) occur because the brain is more dependent on salvage pathways. IMP to XMP conversion is catalysed by IMP dehydrogenase. Hypoxanthine to xanthine is catalysed by xanthine oxidase. AICAR transformation is a step in de novo synthesis.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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