is the general name of an enzyme
family with peroxidase
activity whose main biological role is to protect the organism from oxidative damage. The biochemical function of glutathione peroxidase is to reduce lipid hydroperoxides
to their corresponding alcohols
and to reduce free hydrogen peroxide
There are several isozymes encoded by different genes, which vary in celullar location and substrate specificity. Glutathione peroxidase 1 is the most abundant version, found in the cytoplasm of nearly all mammalian tissues, whose preferred substrate is hydrogen peroxide.
An example reaction that glutathione peroxidase catalyzes
- 2GSH + H2O2 → GS–SG + 2H2O,
where GSH represents reduced monomeric glutathione, and GS–SG represents glutathione disulfide.
Glutathione reductase then reduces the oxidized glutathione to complete the cycle:
- GS–SG + NADPH + H+ → 2 GSH + NADP+.
Glutathione peroxidase is a selenium
-containing tetrameric glycoprotein
, that is, a molecule with four selenocysteine amino acid
residues. As the integrity of the cellular and subcellular membranes depends heavily on glutathione
peroxidase, the antioxidative
protective system of glutathione peroxidase itself depends heavily on the presence of selenium.
GP reaction mechanism
The mechanism is at the Selenocystein site, which is in a Se(-) form as resting state. This is oxidized by the peroxide to SeOH which is then trapped by a GSH molecule to Se-SG and by another GSH molecule to Se(-) again, releasing a GS-SG by-product.
GP in other animals
Mice genetically engineered to lack glutathione peroxidase 1 (Gpx1 knockout mice) are phenotypically normal, indicating that this enzyme is not critical for life.
However, glutathione peroxidase 4 knockout (Gpx4 knockout) mice die during early embryonic development.
There is some evidence that reduced levels of glutathione peroxidase 4 can increase life expectancy in mice.
The bovine erythrocyte enzyme has a molecular weight of 84 kDa.
Glutathione peroxidase was discovered in 1957 by Gordon C. Mills.