A 20-year-old man has recurrent hemolytic crises triggered by infections and oxidant drugs. Peripheral smear shows Heinz bodies on supravital staining. Enzyme assay confirms the diagnosis. Which step in the hexose monophosphate shunt is directly impaired in this condition?

• A Phosphofructokinase-mediated phosphorylation
• B Pyruvate kinase-mediated ATP production
• C Transketolase-mediated carbon rearrangement
• D Glucose-6-phosphate dehydrogenase-mediated NADPH generation ✓

Explanation

G6PD deficiency impairs the first step of the hexose monophosphate (HMP) shunt, which normally reduces NADP+ to NADPH. NADPH is required to regenerate glutathione (via glutathione reductase), which protects red cells from oxidant damage. Without NADPH, oxidized hemoglobin precipitates as Heinz bodies, and the membrane becomes rigid, causing extravascular and intravascular hemolysis. Pyruvate kinase deficiency causes a separate hemolytic anemia via ATP depletion.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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