Glutathione peroxidase

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Function

Glutathione peroxidase (GPX) reduces lipid hydroperoxides to alcohols and free hydrogen peroxide to water. Thus, GPX protects the organism from oxidative damage[1]. There are several isozymes of GPX. Eight isozymes have been found in human.

  • GPX1 is found in the cytoplasm and reduces hydrogen peroxide[2].
  • GPX2 is intestinal and extracellular and is the major oxidative stress-inducible GPX in lungs.
  • GPX3 is abundant in plasma.
  • GPX4 substrate is lipid hydroxyperoxide[3].
  • GPX5 protects spermatozoa from effects of lipid peroxidation[4].
  • GPX7 is a strong neutralizer of H2O2 independent of glutathione[5].

Relevance

Low levels of GPX are found in patients of vitiligo, type 2 diabetes and relapsing multiple sclerosis. There is age-related decrease of GPX activity and hence in antioxidant activity. GPX3 is a candidate of inducing anticancer drug resistance in ovarian clear cell adenocarcinoma[6]. GPX4 protects cortical neurons from oxidative injury[7]GPX7 has potential tumor suppressor function[8].


Glutatione peroxidase 1 complex with glycerol and ammonium ion, 3e0u

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3D Structures of glutathione peroxidase

Updated on 25-June-2024

References

  1. Arthur JR. The glutathione peroxidases. Cell Mol Life Sci. 2000 Dec;57(13-14):1825-35. PMID:11215509
  2. Lei XG, Cheng WH, McClung JP. Metabolic regulation and function of glutathione peroxidase-1. Annu Rev Nutr. 2007;27:41-61. PMID:17465855 doi:http://dx.doi.org/10.1146/annurev.nutr.27.061406.093716
  3. Ran Q, Liang H, Ikeno Y, Qi W, Prolla TA, Roberts LJ 2nd, Wolf N, Van Remmen H, Richardson A. Reduction in glutathione peroxidase 4 increases life span through increased sensitivity to apoptosis. J Gerontol A Biol Sci Med Sci. 2007 Sep;62(9):932-42. PMID:17895430
  4. Hall L, Williams K, Perry AC, Frayne J, Jury JA. The majority of human glutathione peroxidase type 5 (GPX5) transcripts are incorrectly spliced: implications for the role of GPX5 in the male reproductive tract. Biochem J. 1998 Jul 1;333 ( Pt 1):5-9. PMID:9639555
  5. Peng D, Belkhiri A, Hu T, Chaturvedi R, Asim M, Wilson KT, Zaika A, El-Rifai W. Glutathione peroxidase 7 protects against oxidative DNA damage in oesophageal cells. Gut. 2012 Sep;61(9):1250-60. doi: 10.1136/gutjnl-2011-301078. Epub 2011 Dec 9. PMID:22157330 doi:http://dx.doi.org/10.1136/gutjnl-2011-301078
  6. Saga Y, Ohwada M, Suzuki M, Konno R, Kigawa J, Ueno S, Mano H. Glutathione peroxidase 3 is a candidate mechanism of anticancer drug resistance of ovarian clear cell adenocarcinoma. Oncol Rep. 2008 Dec;20(6):1299-303. PMID:19020706
  7. Ran Q, Gu M, Van Remmen H, Strong R, Roberts JL, Richardson A. Glutathione peroxidase 4 protects cortical neurons from oxidative injury and amyloid toxicity. J Neurosci Res. 2006 Jul;84(1):202-8. PMID:16673405 doi:http://dx.doi.org/10.1002/jnr.20868
  8. Peng D, Hu T, Soutto M, Belkhiri A, Zaika A, El-Rifai W. Glutathione peroxidase 7 has potential tumour suppressor functions that are silenced by location-specific methylation in oesophageal adenocarcinoma. Gut. 2014 Apr;63(4):540-51. doi: 10.1136/gutjnl-2013-304612. Epub 2013 Apr 12. PMID:23580780 doi:http://dx.doi.org/10.1136/gutjnl-2013-304612

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Michal Harel

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