glutathione peroxidase
Summary
Glutathione peroxidase (GPx) is a selenium-containing antioxidant enzyme that reduces hydrogen peroxide and lipid peroxides to water and lipid alcohols, respectively, using glutathione (GSH) as the electron donor. It protects red blood cells and other tissues from oxidative damage, working alongside catalase and superoxide dismutase in the cellular antioxidant defense system.
Detail
Glutathione peroxidase catalyzes the reduction of hydrogen peroxide (H2O2) and organic hydroperoxides using reduced glutathione (GSH) as a cofactor, converting it to oxidized glutathione (GSSG). GSSG is then recycled back to GSH by glutathione reductase, which requires NADPH generated primarily via the pentose phosphate pathway (hexose monophosphate shunt). This enzyme is selenium-dependent, making selenium an essential micronutrient for antioxidant defense.
Clinical significance: In G6PD deficiency, decreased NADPH production impairs the regeneration of GSH, reducing glutathione peroxidase's ability to detoxify oxidative stressors (e.g., infections, sulfa drugs, fava beans, antimalarials). This leads to oxidative damage to RBC membranes and hemoglobin, causing Heinz body formation, hemolysis, and bite cells on peripheral smear—classic findings in G6PD deficiency-induced hemolytic anemia.
Glutathione peroxidase is part of a broader antioxidant network: superoxide dismutase converts superoxide radicals to H2O2, which is then neutralized by either catalase (in peroxisomes) or glutathione peroxidase (in cytosol/mitochondria). This system is critical in erythrocytes, which lack mitochondria and rely heavily on the HMP shunt and glutathione pathway for oxidative defense.
Selenium deficiency can impair glutathione peroxidase activity, contributing to conditions like Keshan disease (a cardiomyopathy) in regions with selenium-poor soil.
High-yield boards association: Understanding this pathway is essential for explaining the pathophysiology of G6PD deficiency, a classic X-linked recessive condition tested extensively on Step 1.
Sources
- First Aid for the USMLE Step 1
- Lippincott Illustrated Reviews: Biochemistry
- Robbins and Cotran Pathologic Basis of Disease
Reviewed by AnkiBoss editorial — medical student review. Information here is for study reference only and is not medical advice. Spotted an error? Let us know.