Which pathway protects RBCs from oxidative damage?

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Multiple Choice

Which pathway protects RBCs from oxidative damage?

Red blood cells rely on the hexose-monophosphate shunt to defend against oxidative stress. This pathway generates NADPH, which keeps glutathione in its reduced form (GSH). Reduced glutathione is essential for detoxifying reactive oxygen species: glutathione peroxidase uses GSH to reduce hydrogen peroxide and lipid peroxides, converting GSH to its oxidized form (GSSG), which is then regenerated back to GSH by glutathione reductase using NADPH from the same pathway. Since RBCs lack mitochondria, they depend on this pentose phosphate pathway as their main source of NADPH for antioxidant defense. When this pathway is impaired, as in G6PD deficiency, red cells become vulnerable to oxidative damage and hemolysis. The other pathways don’t provide this broad NADPH-driven antioxidant protection: Embden-Meyerhof (glycolysis) mainly makes ATP, the Luebering-Rapoport shunt adjusts 2,3-BPG, and the methemoglobin reductase system uses NADH to reduce methemoglobin but does not furnish NADPH for general oxidative stabilization.

Red blood cells rely on the hexose-monophosphate shunt to defend against oxidative stress. This pathway generates NADPH, which keeps glutathione in its reduced form (GSH). Reduced glutathione is essential for detoxifying reactive oxygen species: glutathione peroxidase uses GSH to reduce hydrogen peroxide and lipid peroxides, converting GSH to its oxidized form (GSSG), which is then regenerated back to GSH by glutathione reductase using NADPH from the same pathway. Since RBCs lack mitochondria, they depend on this pentose phosphate pathway as their main source of NADPH for antioxidant defense. When this pathway is impaired, as in G6PD deficiency, red cells become vulnerable to oxidative damage and hemolysis. The other pathways don’t provide this broad NADPH-driven antioxidant protection: Embden-Meyerhof (glycolysis) mainly makes ATP, the Luebering-Rapoport shunt adjusts 2,3-BPG, and the methemoglobin reductase system uses NADH to reduce methemoglobin but does not furnish NADPH for general oxidative stabilization.

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