Glutathione peroxidase (GPx) (GPx)

Glutathione peroxidase (GPx) is a family of enzymes (GPx1–GPx8) that serve as a primary defense against oxidative stress by catalyzing the reduction of hydrogen peroxide and organic hydroperoxides to water or alcohols (UniProt P07203, P36969). These enzymes typically utilize glutathione (GSH) as a reducing agent and often contain a selenocysteine residue at the active site, making selenium an essential micronutrient for their function (PubMed: 29053118). GPx4 is particularly notable for its unique ability to reduce phospholipid hydroperoxides within membranes, thereby acting as a master regulator of ferroptosis, a form of regulated cell death (PubMed: 24439385). In clinical contexts, GPx deficiency or dysfunction is associated with cardiovascular disease, neurodegeneration, and chronic inflammation, while its overexpression can contribute to chemoresistance in cancer (StatPearls: NBK559250). Therapeutic approaches include the use of GPx mimics like ebselen to treat stroke or hearing loss, and the development of GPx4 inhibitors to induce cell death in resistant tumors (PubChem CID 3194). The broader antioxidant defense system mentioned in the query encompasses GPx along with superoxide dismutase, catalase, and various non-enzymatic antioxidants that collectively maintain cellular redox homeostasis.

Other names

GSHPxSelenoprotein GPxGlutathione:hydrogen-peroxide oxidoreductase

GPx mimics like ebselen catalyze the reduction of hydroperoxides using glutathione as a cofactor (PubChem CID 3194). GPx4 inhibitors like RSL3 covalently bind the active site selenocysteine, preventing the reduction of lipid hydroperoxides and thereby inducing ferroptotic cell death (PubMed: 24439385).