Which enzyme deficiency predisposes to oxidative stress–induced intravascular hemolysis?

• A. Pyruvate kinase
• B. Hexokinase
• C. Glucose-6-phosphate dehydrogenase
• D. Adenylate kinase

Answer: (C)

Red blood cells rely on the pentose phosphate pathway to generate NADPH, which keeps glutathione in the reduced form to neutralize reactive oxygen species. When the enzyme that starts this pathway is deficient, NADPH production falls, so reduced glutathione can’t efficiently detoxify oxidative stress. Under oxidant challenges such as certain drugs, infections, or fava beans, this leads to oxidative damage to the red cell membrane and hemoglobin, causing intravascular hemolysis with Heinz bodies. Other enzyme defects mentioned mainly affect energy metabolism or membrane stability rather than the oxidative defense powered by NADPH, so they don’t specifically predispose to oxidative-stress–induced intravascular hemolysis.