Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzyme deficiency worldwide. Oxidative stress triggers hemolytic crises in G6PD-deficient erythrocytes because red cells cannot regenerate NADPH. Which downstream antioxidant molecule's activity is most directly dependent on NADPH availability?
- A Glutathione peroxidase, via glutathione reductase's requirement for NADPH to regenerate reduced glutathione (GSH) ✓
- B Catalase
- C Superoxide dismutase (SOD)
- D Vitamin E recycling via NADPH oxidase
Explanation
NADPH generated by G6PD in the HMP shunt is required by glutathione reductase to reduce oxidized glutathione (GSSG) back to reduced glutathione (GSH). GSH is the substrate for glutathione peroxidase, which neutralizes H2O2 and lipid peroxides. In G6PD-deficient erythrocytes, oxidative stress depletes GSH; accumulating H2O2 oxidizes hemoglobin sulfhydryls, forming Heinz bodies that damage the membrane. The resulting hemolytic anemia is triggered by oxidant drugs (primaquine, dapsone), fava beans (vicine, convicine), and infections. Erythrocytes are uniquely vulnerable because they lack mitochondria for alternative NADPH production.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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