Editing Antioxidant (section)

==== Superoxide dismutase, catalase, and peroxiredoxins ====
[[Superoxide dismutase]]s (SODs) are a class of closely related enzymes that catalyze the breakdown of the superoxide anion into oxygen and hydrogen peroxide.<ref>{{Cite journal |vauthors=Zelko IN, Mariani TJ, Folz RJ |date=August 2002 |title=Superoxide dismutase multigene family: a comparison of the CuZn-SOD (SOD1), Mn-SOD (SOD2), and EC-SOD (SOD3) gene structures, evolution, and expression |journal=Free Radical Biology & Medicine |volume=33 |issue=3 |pages=337–49 |doi=10.1016/S0891-5849(02)00905-X |pmid=12126755}}</ref><ref name="Bannister">{{Cite journal |vauthors=Bannister JV, Bannister WH, Rotilio G |year=1987 |title=Aspects of the structure, function, and applications of superoxide dismutase |journal=CRC Critical Reviews in Biochemistry |volume=22 |issue=2 |pages=111–80 |doi=10.3109/10409238709083738 |pmid=3315461}}</ref> SOD enzymes are present in almost all aerobic cells and in extracellular fluids.<ref>{{Cite journal |vauthors=Johnson F, Giulivi C |year=2005 |title=Superoxide dismutases and their impact upon human health |journal=Molecular Aspects of Medicine |volume=26 |issue=4–5 |pages=340–52 |doi=10.1016/j.mam.2005.07.006 |pmid=16099495}}</ref> Superoxide dismutase enzymes contain metal ion cofactors that, depending on the isozyme, can be copper, zinc, [[manganese]] or iron. {{Better source needed|reason=The current source is insufficiently reliable ([[WP:NOTRS]]).|date=April 2025}}In humans, the copper/zinc SOD is present in the [[cytosol]], while manganese SOD is present in the [[mitochondrion]].<ref name="Bannister" /> There also exists a third form of SOD in [[extracellular fluid]]s, which contains copper and zinc in its active sites.<ref>{{Cite journal |vauthors=Nozik-Grayck E, Suliman HB, Piantadosi CA |date=December 2005 |title=Extracellular superoxide dismutase |journal=The International Journal of Biochemistry & Cell Biology |volume=37 |issue=12 |pages=2466–71 |doi=10.1016/j.biocel.2005.06.012 |pmid=16087389}}</ref> The mitochondrial isozyme seems to be the most biologically important of these three, since mice lacking this enzyme die soon after birth.<ref>{{Cite journal |vauthors=Melov S, Schneider JA, Day BJ, Hinerfeld D, Coskun P, Mirra SS, Crapo JD, Wallace DC |date=February 1998 |title=A novel neurological phenotype in mice lacking mitochondrial manganese superoxide dismutase |journal=Nature Genetics |volume=18 |issue=2 |pages=159–63 |doi=10.1038/ng0298-159 |pmid=9462746 |s2cid=20843002}}</ref> In contrast, the mice lacking copper/zinc SOD (Sod1) are viable but have numerous pathologies and a reduced lifespan (see article on [[superoxide]]), while mice without the extracellular SOD have minimal defects (sensitive to [[hyperoxia]]).<ref name="Magnenat" /><ref>{{Cite journal |vauthors=Reaume AG, Elliott JL, Hoffman EK, Kowall NW, Ferrante RJ, Siwek DF, Wilcox HM, Flood DG, Beal MF, Brown RH, Scott RW, Snider WD |date=May 1996 |title=Motor neurons in Cu/Zn superoxide dismutase-deficient mice develop normally but exhibit enhanced cell death after axonal injury |journal=Nature Genetics |volume=13 |issue=1 |pages=43–7 |doi=10.1038/ng0596-43 |pmid=8673102 |s2cid=13070253}}</ref> In plants, SOD isozymes are present in the cytosol and mitochondria, with an iron SOD found in [[chloroplast]]s that is absent from [[vertebrate]]s and [[yeast]].<ref>{{Cite journal |vauthors=Van Camp W, Inzé D, Van Montagu M |year=1997 |title=The regulation and function of tobacco superoxide dismutases |url=https://biblio.ugent.be/publication/183882/file/4172144 |journal=Free Radical Biology & Medicine |volume=23 |issue=3 |pages=515–20 |doi=10.1016/S0891-5849(97)00112-3 |pmid=9214590}}</ref>

[[Catalase]]s are enzymes that catalyse the conversion of hydrogen peroxide to water and oxygen, using either an iron or manganese cofactor.<ref>{{Cite journal |vauthors=Chelikani P, Fita I, Loewen PC |date=January 2004 |title=Diversity of structures and properties among catalases |url=https://digital.csic.es/bitstream/10261/111097/1/accesoRestringido.pdf |journal=Cellular and Molecular Life Sciences |type=Submitted manuscript |volume=61 |issue=2 |pages=192–208 |doi=10.1007/s00018-003-3206-5 |pmc=11138816 |pmid=14745498 |s2cid=4411482 |hdl=10261/111097}}</ref><ref>{{Cite journal |vauthors=Zámocký M, Koller F |year=1999 |title=Understanding the structure and function of catalases: clues from molecular evolution and in vitro mutagenesis |journal=Progress in Biophysics and Molecular Biology |volume=72 |issue=1 |pages=19–66 |doi=10.1016/S0079-6107(98)00058-3 |pmid=10446501 |doi-access=free}}</ref> This protein is localized to [[peroxisome]]s in most [[eukaryote|eukaryotic]] cells.<ref>{{Cite journal |vauthors=del Río LA, Sandalio LM, Palma JM, Bueno P, Corpas FJ |date=November 1992 |title=Metabolism of oxygen radicals in peroxisomes and cellular implications |journal=Free Radical Biology & Medicine |volume=13 |issue=5 |pages=557–80 |doi=10.1016/0891-5849(92)90150-F |pmid=1334030}}</ref> Catalase is an unusual enzyme since, although hydrogen peroxide is its only substrate, it follows a [[enzyme kinetics|ping-pong mechanism]]. Here, its cofactor is oxidised by one molecule of hydrogen peroxide and then regenerated by transferring the bound oxygen to a second molecule of substrate.<ref>{{Cite journal |vauthors=Hiner AN, Raven EL, Thorneley RN, García-Cánovas F, Rodríguez-López JN |date=July 2002 |title=Mechanisms of compound I formation in heme peroxidases |journal=Journal of Inorganic Biochemistry |volume=91 |issue=1 |pages=27–34 |doi=10.1016/S0162-0134(02)00390-2 |pmid=12121759}}</ref> Despite its apparent importance in hydrogen peroxide removal, humans with genetic deficiency of catalase&nbsp;— "[[acatalasemia]]"&nbsp;— or mice [[Genetic engineering|genetically engineered]] to lack catalase completely, experience few ill effects.<ref>{{Cite journal |vauthors=Mueller S, Riedel HD, Stremmel W |date=December 1997 |title=Direct evidence for catalase as the predominant H2O2 -removing enzyme in human erythrocytes |journal=Blood |volume=90 |issue=12 |pages=4973–8 |doi=10.1182/blood.V90.12.4973 |pmid=9389716 |doi-access=free}}</ref><ref>{{Cite journal |vauthors=Ogata M |date=February 1991 |title=Acatalasemia |journal=Human Genetics |volume=86 |issue=4 |pages=331–40 |doi=10.1007/BF00201829 |pmid=1999334 |s2cid=264033871}}</ref>

[[Image:Peroxiredoxin.png|thumb|[[Quaternary structure|Decameric]] structure of AhpC, a [[bacterial]] 2-cysteine [[peroxiredoxin]] from ''[[Salmonella enterica|Salmonella typhimurium]]''<ref>{{Cite journal |vauthors=Parsonage D, Youngblood D, Sarma G, Wood Z, Karplus P, Poole L |year=2005 |title=Analysis of the link between enzymatic activity and oligomeric state in AhpC, a bacterial peroxiredoxin |journal=Biochemistry |volume=44 |issue=31 |pages=10583–92 |doi=10.1021/bi050448i |pmc=3832347 |pmid=16060667}} [http://www.rcsb.org/pdb/explore.do?structureId=1YEX PDB 1YEX]</ref>]]

[[Peroxiredoxin]]s are peroxidases that catalyze the reduction of hydrogen peroxide, [[organic peroxide|organic hydroperoxides]], as well as [[peroxynitrite]].<ref>{{Cite journal |vauthors=Rhee SG, Chae HZ, Kim K |date=June 2005 |title=Peroxiredoxins: a historical overview and speculative preview of novel mechanisms and emerging concepts in cell signaling |journal=Free Radical Biology & Medicine |volume=38 |issue=12 |pages=1543–52 |doi=10.1016/j.freeradbiomed.2005.02.026 |pmid=15917183}}</ref> They are divided into three classes: typical 2-cysteine peroxiredoxins; atypical 2-cysteine peroxiredoxins; and 1-cysteine peroxiredoxins.<ref>{{Cite journal |vauthors=Wood ZA, Schröder E, Robin Harris J, Poole LB |date=January 2003 |title=Structure, mechanism and regulation of peroxiredoxins |journal=Trends in Biochemical Sciences |volume=28 |issue=1 |pages=32–40 |doi=10.1016/S0968-0004(02)00003-8 |pmid=12517450}}</ref> These enzymes share the same basic catalytic mechanism, in which a redox-active cysteine (the peroxidatic cysteine) in the [[active site]] is oxidized to a [[sulfenic acid]] by the peroxide substrate.<ref>{{Cite journal |vauthors=Claiborne A, Yeh JI, Mallett TC, Luba J, Crane EJ, Charrier V, Parsonage D |date=November 1999 |title=Protein-sulfenic acids: diverse roles for an unlikely player in enzyme catalysis and redox regulation |journal=Biochemistry |volume=38 |issue=47 |pages=15407–16 |doi=10.1021/bi992025k |pmid=10569923 |s2cid=29055779}}</ref> Over-oxidation of this cysteine residue in peroxiredoxins inactivates these enzymes, but this can be reversed by the action of [[sulfiredoxin]].<ref>{{Cite book |url=https://books.google.com/books?id=gHwEOH7vDmUC |title=Peroxiredoxin Systems |vauthors=Jönsson TJ, Lowther WT |year=2007 |isbn=978-1-4020-6050-2 |series=Subcellular Biochemistry |volume=44 |pages=115–41 |chapter=The peroxiredoxin repair proteins |doi=10.1007/978-1-4020-6051-9_6 |pmc=2391273 |pmid=18084892}}</ref> Peroxiredoxins seem to be important in antioxidant metabolism, as mice lacking peroxiredoxin 1 or 2 have shortened lifespans and develop [[hemolytic anaemia]], while plants use peroxiredoxins to remove hydrogen peroxide generated in chloroplasts.<ref>{{Cite journal |vauthors=Neumann CA, Krause DS, Carman CV, Das S, Dubey DP, Abraham JL, Bronson RT, Fujiwara Y, Orkin SH, Van Etten RA |date=July 2003 |title=Essential role for the peroxiredoxin Prdx1 in erythrocyte antioxidant defence and tumour suppression |url=https://cloudfront.escholarship.org/dist/prd/content/qt8m75q3ct/qt8m75q3ct.pdf?t=nhvrjt |journal=Nature |volume=424 |issue=6948 |pages=561–5 |bibcode=2003Natur.424..561N |doi=10.1038/nature01819 |pmid=12891360 |s2cid=3570549}}</ref><ref>{{Cite journal |vauthors=Lee TH, Kim SU, Yu SL, Kim SH, Park DS, Moon HB, Dho SH, Kwon KS, Kwon HJ, Han YH, Jeong S, Kang SW, Shin HS, Lee KK, Rhee SG, Yu DY |date=June 2003 |title=Peroxiredoxin II is essential for sustaining life span of erythrocytes in mice |url=http://www.bloodjournal.org/cgi/content/full/101/12/5033 |journal=Blood |volume=101 |issue=12 |pages=5033–8 |doi=10.1182/blood-2002-08-2548 |pmid=12586629 |doi-access=free}}</ref><ref>{{Cite journal |vauthors=Dietz KJ, Jacob S, Oelze ML, Laxa M, Tognetti V, de Miranda SM, Baier M, Finkemeier I |year=2006 |title=The function of peroxiredoxins in plant organelle redox metabolism |journal=Journal of Experimental Botany |volume=57 |issue=8 |pages=1697–709 |doi=10.1093/jxb/erj160 |pmid=16606633 |doi-access=free}}</ref>