In glucose-6-phosphate dehydrogenase (G6PD) deficiency, which of the following molecular events is the proximate cause of erythrocyte hemolysis during oxidant stress?

• A Direct inhibition of hemoglobin synthesis by oxidized NADP+
• B Accumulation of glucose-6-phosphate causing osmotic lysis
• C Depletion of NADPH leading to oxidation of glutathione and accumulation of Heinz bodies ✓
• D Depletion of ATP due to shunting of glycolysis away from the Embden-Meyerhof pathway

Explanation

G6PD is the rate-limiting enzyme of the hexose monophosphate shunt, generating NADPH. NADPH maintains glutathione in its reduced (GSH) form, which neutralizes oxidative radicals. In G6PD-deficient cells, NADPH depletion means glutathione cannot be regenerated, causing oxidized hemoglobin to precipitate as Heinz bodies; these rigid inclusions cause mechanical hemolysis as RBCs traverse the spleen. Glucose-6-phosphate does not accumulate osmotically; ATP is generated mainly by glycolysis, which is not directly impaired.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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