Glutathione peroxidase

glutathione peroxidase 1 Identifiers Symbol GPX1 Entrez 2876 HUGO 4553 OMIM 138320 RefSeq NM_000581 UniProt P07203 Other data EC number 1.11.1.9 Locus Chr. 3 p21.3

glutathione peroxidase 3 (plasma) Identifiers Symbol GPX3 Entrez 2878 HUGO 4555 OMIM 138321 RefSeq NM_002084 UniProt P22352 Other data EC number 1.11.1.9 Locus Chr. 5 q23

glutathione peroxidase 5 (epididymal androgen-related protein) Identifiers Symbol GPX5 Entrez 2880 HUGO 4557 OMIM 603435 RefSeq NM_001509 UniProt O75715 Other data EC number 1.11.1.9 Locus Chr. 6 p21.32

glutathione peroxidase 6 (olfactory) Identifiers Symbol GPX6 Entrez 257202 HUGO 4558 OMIM 607913 RefSeq NM_182701 UniProt P59796 Other data EC number 1.11.1.9 Locus Chr. 6 p21

Glutathione peroxidase (PDB 1GP1, EC 1.11.1.9) 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 to water.

Isozymes

There are several isozymes encoded by different genes, which vary in celullar location and substrate specificity. Glutathione peroxidase 1 (GPx1) is the most abundant version, found in the cytoplasm of nearly all mammalian tissues, whose preferred substrate is hydrogen peroxide. Glutathione peroxidase 4 (GPx4) has a high preference for lipid hydroperoxides; it is expressed in nearly every mammalian cell, though at much lower levels. Glutathione peroxidase 2 is an intestinal and extracellular enzyme, while glutathione peroxidase 3 is extracellular, especially aboundant in plasma^[1]. So far, eight different isoforms of glutathione peroxidase (GPx1-8) have been identified in humans.

Reaction

An example reaction that glutathione peroxidase catalyzes is:

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⁺.

Structure

Mammalian GPx1, GPx2, GPx3, and GPx4 have been shown to be selenium-containing enzymes, whereas GPx6 is a selenoprotein in humans with cysteine-containing homologues in rodents. GPx1, GPx2, and GPx3 are homotetrameric proteins, whereas GPx4 has a monomeric structure. 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.

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.

Species distribution

Mice genetically engineered to lack glutathione peroxidase 1 (Gpx1 knockout mice) are grossly phenotypically normal and have a normal lifespan, indicating that this enzyme is not critical for life. However, Gpx1 -/- mice develop cataracts at an early age and exhibit defects in muscle satelite cell proliferation.^[1]

However, glutathione peroxidase 4 knockout mice die during early embryonic development.^[1]

There is some evidence that reduced levels of glutathione peroxidase 4 can increase life expectancy in mice.^[2]

No information is available on knockouts of the other isozymes.

The bovine erythrocyte enzyme has a molecular weight of 84 kDa.

Discovery

Glutathione peroxidase was discovered in 1957 by Gordon C. Mills.^[3]

References

See also

• Glutathione reductase
• Selenium deficiency