Glutathione peroxidase

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].

3D Structures of glutathione peroxidase3D Structures of glutathione peroxidase

Updated on 25-June-2024

ReferencesReferences

↑ Arthur JR. The glutathione peroxidases. Cell Mol Life Sci. 2000 Dec;57(13-14):1825-35. PMID:11215509
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Michal Harel

[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

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]