G6PD deficiency predisposes patients to haemolytic anaemia upon oxidant exposure (primaquine, fava beans, infections). The underlying biochemical defect is inability to regenerate NADPH because G6PD is the rate-limiting enzyme of which pathway?

• A Hexose monophosphate (HMP) shunt / pentose phosphate pathway, oxidative branch ✓
• B Glycolysis (Embden-Meyerhof pathway)
• C Glucuronic acid pathway for ascorbate synthesis
• D Galactose metabolism (Leloir pathway)

Explanation

The oxidative branch of the pentose phosphate pathway (HMP shunt) converts glucose-6-phosphate → 6-phosphoglucono-delta-lactone using G6PD, generating NADPH. NADPH is the essential reductant for glutathione reductase to maintain GSH, which in turn reduces H2O2 via glutathione peroxidase. Red blood cells rely entirely on the HMP shunt for NADPH because they lack mitochondria. In G6PD deficiency, oxidant stress depletes GSH, oxidative damage to Hb forms Heinz bodies, and RBCs lyse (extravascular haemolysis). Glycolysis produces NADH, not NADPH. The glucuronic acid pathway and Leloir pathway are unrelated to NADPH production from glucose.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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