G6PD (glucose-6-phosphate dehydrogenase) deficiency renders erythrocytes vulnerable to oxidative haemolysis. The key mechanism is the depletion of which molecule that normally protects against oxidative stress?

• A ATP from reduced glycolytic capacity, impairing the Na+/K+-ATPase and causing osmotic haemolysis
• B NADH from the pentose phosphate pathway, reducing methaemoglobin back to haemoglobin via methaemoglobin reductase
• C Reduced glutathione (GSH) directly, because G6PD is required for the last step of glutathione synthesis
• D NADPH (reduced nicotinamide adenine dinucleotide phosphate), which is required to regenerate reduced glutathione (GSH) via glutathione reductase to neutralise H2O2 and free radicals ✓

Explanation

G6PD catalyses the first step of the hexose monophosphate (pentose phosphate) pathway, producing NADPH. Erythrocytes lack mitochondria and depend entirely on the HMP shunt for NADPH generation. NADPH is essential for reducing oxidised glutathione (GSSG) back to GSH via glutathione reductase. GSH, in turn, reduces H2O2 (via glutathione peroxidase) and other reactive oxygen species. In G6PD deficiency, oxidative stressors (primaquine, dapsone, fava beans, infections) overwhelm the limited GSH reserve, causing oxidative denaturation of Hb (Heinz bodies), membrane lipid peroxidation, and haemolysis. NADPH is the key product; G6PD does not directly synthesise GSH.

Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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