In erythrocytes, the HMP shunt (pentose phosphate pathway) is essential for protecting against oxidative hemolysis. G6PD deficiency leads to hemolysis when triggered by oxidative stress. Which molecule directly protects hemoglobin from oxidative denaturation in normal RBCs?

• A NADH produced by the HMP shunt, which reduces methemoglobin back to oxyhemoglobin
• B Reduced glutathione (GSH), regenerated by glutathione reductase using NADPH produced by G6PD in the HMP shunt ✓
• C 2,3-BPG, which stabilises deoxyhemoglobin and prevents oxidative denaturation by reducing hemoglobin affinity for reactive oxygen species
• D Catalase in erythrocytes, which directly detoxifies superoxide radicals generated during hemoglobin oxidation

Explanation

The HMP shunt generates NADPH via G6PD. NADPH is used by glutathione reductase to regenerate GSH from GSSG. GSH is then used by glutathione peroxidase to detoxify hydrogen peroxide (H2O2 + 2GSH → GSSG + 2H2O), protecting hemoglobin and other erythrocyte proteins from oxidative damage. In G6PD deficiency, NADPH is depleted, GSH cannot be regenerated, and oxidative stress causes Heinz body formation and hemolysis. NADPH (not NADH) is the key product. 2,3-BPG regulates oxygen affinity, not oxidative protection.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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