A patient with G6PD deficiency develops hemolysis after eating fava beans. The key biochemical sequence linking G6PD deficiency to erythrocyte destruction is:

• A Divicine from fava beans directly inhibits spectrin in the red cell membrane, causing premature lysis
• B G6PD deficiency blocks the HMP shunt, elevating glucose-6-phosphate which is converted to toxic sorbitol in erythrocytes
• C NADPH deficiency impairs superoxide dismutase activity, directly allowing superoxide to lyse red cell membranes
• D G6PD deficiency reduces NADPH, impairing glutathione reductase, leaving GSH depleted and Hb susceptible to oxidative denaturation to Heinz bodies ✓

Explanation

Erythrocytes rely entirely on the HMP shunt for NADPH production (no mitochondria). NADPH is essential to reduce oxidized glutathione (GSSG) back to GSH via glutathione reductase. GSH neutralizes oxidative stress from fava bean-derived divicine/isouramil by GSH peroxidase. In G6PD-deficient cells, NADPH is inadequate, GSH remains oxidized, and oxidative damage denatures hemoglobin to Heinz bodies. Heinz bodies attach to the cell membrane, causing rigid cells to be trapped and destroyed in the spleen (extravascular hemolysis). SOD does not use NADPH directly.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.