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Subsequently, over time or after chronic stress, RBC may exhaust their supply of reduced GSH, thereby promoting the susceptibility of GPx-1 to irreversible oxidation and loss of the Sec active site. Previous studies in keratinocytes indicated that adequate intracellular stores of GSH protect against peroxide-mediated loss of GPx-1 activity, as addition of GSH to cultures minimized enzymatic inactivation of GPx-1 by exposure to high concentrations of peroxides, whereas buthionine sulfoximine, an inhibitor of GSH biosynthesis, augmented sensitivity to peroxide-induced GPx-1 inactivation In contrast, GPxdeficient mice on a high-fat diet are spared from insulin resistance, and antioxidants make them less sensitive to insulin
