A patient with hemolytic anemia shows no Heinz bodies, normal G6PD activity, and normal hemoglobin electrophoresis. Erythrocyte pyruvate kinase (PK) activity is markedly reduced. Which specific metabolic consequence explains the hemolysis in PK deficiency?

• A Excess NADH from blocked lactate dehydrogenase oxidizes hemoglobin
• B Accumulation of 2,3-BPG at toxic levels directly oxidizes membrane lipids
• C Deficiency of NADPH leaves glutathione reduced, destabilizing the membrane
• D ATP depletion from blocked substrate-level phosphorylation impairs Na/K-ATPase, causing osmotic lysis ✓

Explanation

Pyruvate kinase catalyzes the final ATP-generating step of glycolysis (PEP → pyruvate, producing 2 ATP/glucose). Erythrocytes are entirely dependent on glycolysis for ATP since they lack mitochondria. PK deficiency causes severe ATP depletion, impairing the Na+/K+-ATPase pump, leading to osmotic influx, swelling, and lysis. Note: 2,3-BPG actually accumulates due to the block (not to toxic levels) and paradoxically causes a right-shift in the oxygen dissociation curve.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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