Glutathione peroxidase

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Glutathione peroxidase
Crystallographic structure of bovine glutathione peroxidase 1.[1]
EC number
CAS number 9013-66-5
IntEnz IntEnz view
ExPASy NiceZyme view
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Gene Ontology AmiGO / EGO
Glutathione peroxidase
Symbol GSHPx
Pfam PF00255
InterPro IPR000889
SCOP 1gp1



Several isozymes are encoded by different genes, which vary in cellular 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)


The main reaction that glutathione peroxidase catalyzes is:

2GSH + H2O2 → GS–SG + 2H2O

where GSH represents reduced monomeric glutathione, and GS–SG represents glutathione disulfide. The mechanism involves oxidation of the selenol of a selenocysteine residue by hydrogen peroxide. This process gives the derivative with a seleninic acid (RSeOH) group. The selenenic acid is then converted back to the selenol by a two step process that begins with reaction with GSH to form the GS-SeR and water. A second GSH molecule reduces the GS-SeR intermediate back to the selenol, releasing GS-SG as the by-product. A simplified representation is shown below:[3]

RSeH + H2O2 → RSeOH + H2O
RSeOH + GSH → GS-SeR + H2O

Glutathione reductase then reduces the oxidized glutathione to complete the cycle:

GS–SG + NADPH + H+ → 2 GSH + NADP+.


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, its antioxidative protective system itself depends heavily on the presence of selenium.

Species distribution[edit]

Mice genetically engineered to lack glutathione peroxidase 1 (Gpx1 knockout mice) are grossly phenotypically normal and have normal lifespans, indicating 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]

Some evidence, though, indicates reduced levels of glutathione peroxidase 4 can increase life expectancy in mice.[4]

No information is available on knockouts of the other isozymes.

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


Glutathione peroxidase was discovered in 1957 by Gordon C. Mills.[5]

Human proteins containing this domain[edit]



  1. ^ 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. 
  3. ^ Krishna P. Bhabak, Govindasamy Mugesh "Functional Mimics of Glutathione Peroxidase: Bioinspired Synthetic Antioxidants" Acc. Chem. Res., 2010, 43 (11), pp 1408–1419. doi:10.1021/ar100059g
  4. ^ 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. doi:10.1093/gerona/62.9.932. PMID 17895430. 
  5. ^ 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. 

See also[edit]