In the HMP shunt (pentose phosphate pathway), the oxidative phase generates NADPH and ribose-5-phosphate. A patient with G6PD deficiency is given primaquine. Haemolysis occurs because:

• A Ribose-5-phosphate depletion impairs nucleotide synthesis in RBCs
• B G6PD deficiency impairs glycolysis in RBCs, reducing ATP production
• C Primaquine directly inhibits catalase, allowing superoxide accumulation
• D NADPH deficiency impairs glutathione reductase from regenerating reduced glutathione, allowing H2O2 to accumulate and oxidise haemoglobin ✓

Explanation

RBCs lack mitochondria and rely entirely on the HMP shunt for NADPH. NADPH maintains glutathione in the reduced form (GSH) via glutathione reductase. GSH reduces H2O2 via glutathione peroxidase and protects haemoglobin and membrane proteins from oxidative damage. In G6PD deficiency, the oxidative phase of HMP shunt is impaired, NADPH is depleted, GSH cannot be regenerated, and primaquine-generated oxidative stress causes H2O2 accumulation. This oxidises haemoglobin to methaemoglobin/Heinz bodies and damages RBC membranes causing intravascular haemolysis. G6PD does not affect glycolysis, which uses a different glucose-6-phosphate pathway. Ribose-5-phosphate depletion is not the mechanism of haemolysis.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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