Glutathione peroxidase
| Glutathione peroxidase | |||||||
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| Crystallographic structure of bovine glutathione peroxidase 1.[1] | |||||||
| Identifiers | |||||||
| EC number | 1.11.1.9 | ||||||
| CAS number | 9013-66-5 | ||||||
| Databases | |||||||
| IntEnz | IntEnz view | ||||||
| BRENDA | BRENDA entry | ||||||
| ExPASy | NiceZyme view | ||||||
| KEGG | KEGG entry | ||||||
| MetaCyc | metabolic pathway | ||||||
| PRIAM | profile | ||||||
| PDB structures | RCSB PDB PDBe PDBsum | ||||||
| Gene Ontology | AmiGO / EGO | ||||||
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| Identifiers | |||||||||
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| Symbol | GSHPx | ||||||||
| Pfam | PF00255 | ||||||||
| InterPro | IPR000889 | ||||||||
| PROSITE | PDOC00396 | ||||||||
| SCOP | 1gp1 | ||||||||
| SUPERFAMILY | 1gp1 | ||||||||
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Glutathione peroxidase (GPx) (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.
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[edit] 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 abundant in plasma.[2] So far, eight different isoforms of glutathione peroxidase (GPx1-8) have been identified in humans.
| Gene | Locus | Enzyme |
|---|---|---|
| GPX1 | Chr. 3 p21.3 | glutathione peroxidase 1 |
| GPX2 | Chr. 14 q24.1 | glutathione peroxidase 2 (gastrointestinal) |
| GPX3 | Chr. 5 q23 | glutathione peroxidase 3 (plasma) |
| GPX4 | Chr. 19 p13.3 | glutathione peroxidase 4 (phospholipid hydroperoxidase) |
| GPX5 | Chr. 6 p21.32 | glutathione peroxidase 5 (epididymal androgen-related protein) |
| GPX6 | Chr. 6 p21 | glutathione peroxidase 6 (olfactory) |
| GPX7 | Chr. 1 p32 | glutathione peroxidase 7 |
| GPX8 | Chr. 5 q11.2 | glutathione peroxidase 8 (putative) |
[edit] 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+.
[edit] 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.
[edit] Reaction mechanism
The mechanism is at the selenocysteine site, which is in a Se(-) form as resting state. This is oxidized by the peroxide to SeOH, which then reacts with a GSH molecule to form GS-Se and water, and then by another GSH molecule to from Se(-) again, releasing GS-SG as the by-product.
[edit] 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 satellite cell proliferation.[2]
However, glutathione peroxidase 4 knockout mice die during early embryonic development.[2]
There is some evidence that reduced levels of glutathione peroxidase 4 can increase life expectancy in mice.[3]
No information is available on knockouts of the other isozymes.
The bovine erythrocyte enzyme has a molecular weight of 84 kDa.
[edit] Role in disease
Genetic polymorphisms in glutathione peroxidase enzymes and their altered expressions and activities are associated with oxidative DNA damage and, as a result, the individual’s risk of cancer susceptibility.[4]
[edit] Discovery
Glutathione peroxidase was discovered in 1957 by Gordon C. Mills.[5]
[edit] Human proteins containing this domain
[edit] References
- ^ PDB 1GP1; Epp O, Ladenstein R, Wendel A (June 1983). "The refined structure of the selenoenzyme glutathione peroxidase at 0.2-nm resolution". Eur. J. Biochem. 133 (1): 51–69. doi:10.1111/j.1432-1033.1983.tb07429.x. PMID 6852035.
- ^ a b c Muller FL, Lustgarten MS, Jang Y, Richardson A, Van Remmen H (August 2007). "Trends in oxidative aging theories". Free Radic. Biol. Med. 43 (4): 477–503. doi:10.1016/j.freeradbiomed.2007.03.034. PMID 17640558.
- ^ Ran Q, Liang H, Ikeno Y (2007). "Reduction in glutathione peroxidase 4 increases life span through increased sensitivity to apoptosis". J. Gerontol. A Biol. Sci. Med. Sci. 62 (9): 932–42. PMID 17895430.
- ^ Khan MA, Tania M, Zhang D, Chen H (2010). "Antioxidant enzymes and cancer". Chin J Cancer Res 22 (2): 87–92. doi:10.1007/s11670-010-0087-7. http://www.springerlink.com/content/4h2277984v0t180k/.
- ^ MILLS GC (November 1957). "Hemoglobin catabolism. I. Glutathione peroxidase, an erythrocyte enzyme which protects hemoglobin from oxidative breakdown". J. Biol. Chem. 229 (1): 189–97. PMID 13491573. http://www.jbc.org/cgi/reprint/229/1/189.
[edit] See also
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