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main menu move to sidebar hide navigation main page contents current events random article about wikipedia contact us contribute help learn to edit community portal recent changes upload file special pages search search appearance donate create account log in personal tools donate create account log in contents move to sidebar hide top 1 reaction 2 human isozymes toggle human isozymes subsection 2 1 structure of isozymes 3 animal models 4 clinical significance 5 evolution 6 determination of activity 7 see also 8 references toggle the table of contents glutathione peroxidase 19 languages العربية bosanski català čeština deutsch español suomi français galego italiano 日本語 bahasa melayu norsk bokmål polski português русский srpskohrvatski српскохрватски српски srpski 中文 edit links article talk english read edit view history tools tools move to sidebar hide actions read edit view history general what links here related changes upload file permanent link page information cite this page get shortened url switch to legacy parser print export download as pdf printable version in other projects wikimedia commons wikidata item appearance move to sidebar hide from wikipedia the free encyclopedia enzyme family protecting the organism from oxidative damages glutathione peroxidase crystallographic structure of bovine glutathione peroxidase 1 1 identifiers ec no 1 11 1 9 cas no 9013 66 5 databases brenda enzyme data expasy nicezyme view kegg enzyme entry metacyc metabolic pathway rhea reactions pdb structures rcsb pdb pdbe pdbsum gene ontology amigo quickgo search pmc articles pubmed articles ncbi proteins protein family glutathione peroxidase identifiers symbol gshpx pfam pf00255 interpro ipr000889 prosite pdoc00396 scop2 1gp1 scope supfam available protein structures pdb 2f8a b 14 128 1gp1 a 19 133 ipr000889 pf00255 ecod pdbsum alphafold ipr000889 pf00255 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 2 the biochemical function of glutathione peroxidase is to reduce lipid hydroperoxides to their corresponding alcohols and to reduce free hydrogen peroxide to water 3 glutathione peroxidase was discovered in 1957 by gordon c mills 4 reaction edit the main reaction that glutathione peroxidase catalyzes is 2 glutathione h 2 o 2 2 h 2 o glutathione disulfide the mechanism involves oxidation of the selenol of a selenocysteine residue by hydrogen peroxide this process gives the derivative with a selenenic acid rseoh group the selenenic acid is then converted back to the selenol by a two step process that begins with reaction with glutathione gsh to form the gs ser and water a second gsh molecule reduces the gs ser intermediate back to the selenol releasing glutathione disulfide gs sg as the by product a simplified representation is shown below 5 rseh h 2 o 2 rseoh h 2 o rseoh gsh gs ser h 2 o gs ser gsh gs sg rseh glutathione reductase then reduces the oxidized glutathione to complete the cycle gs sg nadph h 2 gsh nadp human isozymes edit 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 6 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 structure of isozymes edit 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 animal models edit mice genetically engineered to lack glutathione peroxidase 1 gpx1 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 6 gpx1 mice showed up to 16 db higher auditory brainstem response abr thresholds than control mice after 110 db noise exposure for one hour gpx1 mice had up to 15 db greater noise induced hearing loss compared with control mice 7 mice with knockouts for gpx3 gpx3 or gpx2 gpx2 also develop normally 8 9 however glutathione peroxidase 4 knockout mice die during early embryonic development 6 some evidence though indicates reduced levels of glutathione peroxidase 4 can increase life expectancy in mice 10 clinical significance edit it has been shown that low levels of glutathione peroxidase as measured in the serum may be a contributing factor to vitiligo 11 lower plasma glutathione peroxide levels were also observed in patients with type 2 diabetes with macroalbuminuria and this was correlated to the stage of diabetic nephropathy citation needed in one study the activity of glutathione peroxidase along with other antioxidant enzymes such as superoxide dismutase and catalase was not associated with coronary heart disease risk in women 12 glutathione peroxidase activity was found to be much lower in patients with relapsing remitting multiple sclerosis 13 one study has suggested that glutathione peroxidase and superoxide dismutase polymorphisms play a role in the development of celiac disease 14 the activity of this enzyme has been reported to be decreased in case of copper deficiency in the liver and plasma 15 evolution edit gpxs are a key part of animal including human antioxidant defenses they are also find in bacteria plants and fungi gpx was the first selenoprotein discovered with a highly reactive sec residue at the active site comparison of gpx sequences from all these types of life suggest that the ancestral gpx did not contain selenium instead acquision of sec happened early in animal evolution before the sponges diverged from other animals 16 humans have eight gpx genes but only five of them contain sec gpx1 gpx2 gpx3 gpx4 gpx6 the non existence of sec in gpx7 and gpx8 appears to be universal among animals 16 the loss of sec by replacement with cys in gpx5 was however a relatively recent event that happened after the divergence of humans from rodents rodents have independently lost the sec in gpx6 but kept it in their version of gpx5 human gpx5 and rodent gpx6 retain vestigial secis elements indicative of their past 17 determination of activity edit activity of glutathione peroxidase is measured spectrophotometrically using several methods a direct assay by linking the peroxidase reaction with glutathione reductase with measurement of the conversion of nadph to nadp is widely used 18 the other approach is measuring residual gsh in the reaction with ellman s reagent based on this several procedures for measuring glutathione peroxidase activity were developed using various hydroperoxides as substrates for reduction e g cumene hydroperoxide 19 tert butyl hydroperoxide 20 and hydrogen peroxide 21 the other methods include the use of cuprac reagent with spectrophotometric detection of the reaction product 22 or o phtalaldehyde as a fluorescent reagent 23 see also edit catalase superoxide dismutase glutathione reductase selenium deficiency references edit pdb 1gp1 epp o ladenstein r wendel a june 1983 the refined structure of the selenoenzyme glutathione peroxidase at 0 2 nm resolution european journal of biochemistry 133 1 51 69 doi 10 1111 j 1432 1033 1983 tb07429 x pmid 6852035 muthukumar k nachiappan v december 2010 cadmium induced oxidative stress in saccharomyces cerevisiae indian journal of biochemistry biophysics 47 6 383 7 pmid 21355423 muthukumar k rajakumar s sarkar mn nachiappan v may 2011 glutathione peroxidase3 of saccharomyces cerevisiae protects phospholipids during cadmium induced oxidative stress antonie van leeuwenhoek 99 4 761 71 doi 10 1007 s10482 011 9550 9 pmid 21229313 s2cid 21850794 mills gc november 1957 hemoglobin catabolism i glutathione peroxidase an erythrocyte enzyme which protects hemoglobin from oxidative breakdown the journal of biological chemistry 229 1 189 97 doi 10 1016 s0021 9258 18 70608 x pmid 13491573 bhabak kp mugesh g november 2010 functional mimics of glutathione peroxidase bioinspired synthetic antioxidants accounts of chemical research 43 11 1408 19 doi 10 1021 ar100059g pmid 20690615 1 2 3 muller fl lustgarten ms jang y richardson a van remmen h august 2007 trends in oxidative aging theories free radical biology medicine 43 4 477 503 doi 10 1016 j freeradbiomed 2007 03 034 pmid 17640558 ohlemiller kk mcfadden sl ding dl lear pm ho ys november 2000 targeted mutation of the gene for cellular glutathione peroxidase gpx1 increases noise induced hearing loss in mice journal of the association for research in otolaryngology 1 3 243 54 doi 10 1007 s101620010043 pmc 2504546 pmid 11545230 esworthy rs aranda r martín mg doroshow jh binder sw chu ff september 2001 mice with combined disruption of gpx1 and gpx2 genes have colitis american journal of physiology gastrointestinal and liver physiology 281 3 g848 55 doi 10 1152 ajpgi 2001 281 3 g848 pmid 11518697 s2cid 21615743 olson ge whitin jc hill ke winfrey vp motley ak austin lm et al may 2010 extracellular glutathione peroxidase gpx3 binds specifically to basement membranes of mouse renal cortex tubule cells american journal of physiology renal physiology 298 5 f1244 53 doi 10 1152 ajprenal 00662 2009 pmc 2867408 pmid 20015939 ran q liang h ikeno y qi w prolla ta roberts lj et al september 2007 reduction in glutathione peroxidase 4 increases life span through increased sensitivity to apoptosis the journals of gerontology series a biological sciences and medical sciences 62 9 932 42 doi 10 1093 gerona 62 9 932 pmid 17895430 zedan h abdel motaleb aa kassem nm hafeez ha hussein mr mar 2015 low glutathione peroxidase activity levels in patients with vitiligo journal of cutaneous medicine and surgery 19 2 144 8 doi 10 2310 7750 2014 14076 pmid 25775636 s2cid 32708904 yang s jensen mk rimm eb willett w wu t november 2014 erythrocyte superoxide dismutase glutathione peroxidase and catalase activities and risk of coronary heart disease in generally healthy women a prospective study american journal of epidemiology 180 9 901 8 doi 10 1093 aje kwu195 pmc 4207716 pmid 25156995 socha k kochanowicz j karpińska e soroczyńska j jakoniuk m mariak z borawska mh june 2014 dietary habits and selenium glutathione peroxidase and total antioxidant status in the serum of patients with relapsing remitting multiple sclerosis nutrition journal 13 62 doi 10 1186 1475 2891 13 62 pmc 4080729 pmid 24943732 katar m ozugurlu af ozyurt h benli i february 2014 evaluation of glutathione peroxidase and superoxide dismutase enzyme polymorphisms in celiac disease patients genetics and molecular research 13 1 1030 7 doi 10 4238 2014 february 20 4 inactive 15 july 2025 pmid 24634124 cite journal cs1 maint doi inactive as of july 2025 link hordyjewska anna popiołek łukasz kocot joanna 2014 the many faces of copper in medicine and treatment biometals 27 4 611 621 doi 10 1007 s10534 014 9736 5 pmc 4113679 pmid 24748564 1 2 trenz ts delaix cl turchetto zolet ac zamocky m lazzarotto f margis pinheiro m 12 november 2021 going forward and back the complex evolutionary history of the gpx biology 10 11 1165 doi 10 3390 biology10111165 pmc 8614756 pmid 34827158 castellano sergi novoselov sergey v kryukov gregory v et al 2004 reconsidering the evolution of eukaryotic selenoproteins a novel nonmammalian family with scattered phylogenetic distribution embo reports 5 1 71 7 doi 10 1038 sj embor 7400036 pmc 1298953 pmid 14710190 paglia de valentine wn july 1967 studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase the journal of laboratory and clinical medicine 70 1 158 69 pmid 6066618 zakowski jj tappel al september 1978 a semiautomated system for measurement of glutathione in the assay of glutathione peroxidase analytical biochemistry 89 2 430 6 doi 10 1016 0003 2697 78 90372 x pmid 727443 moin vm 1986 a simple and specific method for determining glutathione peroxidase activity in erythrocytes laboratornoe delo 12 12 724 7 pmid 2434712 razygraev av yushina ad titovich ia august 2018 correction to a method of measuring glutathione peroxidase activity in murine brain application in pharmacological experiment bulletin of experimental biology and medicine 165 4 589 592 doi 10 1007 s10517 018 4219 2 pmid 30121905 s2cid 52038817 ahmed a y aowda s a hadwan m h 2021 a validated method to assess glutathione peroxidase enzyme activity chemical papers 75 12 6625 6637 bibcode 2021chpap 75 6625a doi 10 1007 s11696 021 01826 1 issn 2585 7290 s2cid 236219189 ramos martinez j i launay j m dreux c 1979 a sensitive fluorimetric microassay for the determination of glutathione peroxidase activity application to human blood platelets analytical biochemistry 98 1 154 159 doi 10 1016 0003 2697 79 90720 6 issn 0003 2697 pmid 543550 v t e oxidoreductases peroxidases ec 1 11 1 11 1 1 14 nadh peroxidase nadph peroxidase fatty acid peroxidase catalase cytochrome c peroxidase eosinophil peroxidase glutathione peroxidase gpx 1 2 3 4 5 6 7 8 horseradish peroxidase lactoperoxidase myeloperoxidase thyroid peroxidase deiodinase iodothyronine deiodinase iodotyrosine deiodinase 1 11 1 15 peroxiredoxin 1 2 3 4 5 6 v t e enzymes activity active site binding site catalytic triad oxyanion hole enzyme promiscuity diffusion limited enzyme cofactor enzyme catalysis regulation allosteric regulation cooperativity enzyme inhibitor enzyme activator classification ec number enzyme superfamily enzyme family list of enzymes kinetics enzyme kinetics eadie hofstee diagram hanes woolf plot lineweaver burk plot michaelis menten kinetics types ec1 oxidoreductases list ec2 transferases list ec3 hydrolases list ec4 lyases list ec5 isomerases list ec6 ligases list ec7 translocases list portal biology retrieved from https en wikipedia org w 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