Editing Antioxidant (section)

== Oxidative challenge in biology ==
{{further|Oxidative stress}}

[[Image:L-ascorbic-acid-3D-balls.png|thumb|right|The structure of the antioxidant [[vitamin]] [[ascorbic acid]] (vitamin C)]]

The vast majority of complex [[life|life on Earth]] requires [[oxygen]] for its metabolism, but this same oxygen is a [[reactive oxygen species|highly reactive element]] that can damage living organisms.<ref name=Autox/><ref name="Davies">{{Cite journal |vauthors=Davies KJ |year=1995 |title=Oxidative stress: the paradox of aerobic life |journal=Biochemical Society Symposium |volume=61 |pages=1–31 |doi=10.1042/bss0610001 |pmid=8660387}}</ref> Organisms contain chemicals and [[enzyme]]s that minimize this oxidative damage without interfering with the beneficial effect of oxygen.<ref name="Sies">{{Cite journal |vauthors=Sies H |date=March 1997 |title=Oxidative stress: oxidants and antioxidants |journal=Experimental Physiology |volume=82 |issue=2 |pages=291–5 |doi=10.1113/expphysiol.1997.sp004024 |pmid=9129943 |s2cid=20240552 |doi-access=free}}</ref><ref name="Vertuani">{{Cite journal |vauthors=Vertuani S, Angusti A, Manfredini S |year=2004 |title=The Antioxidants and Pro-Antioxidants Network: an Overview |journal=Current Pharmaceutical Design |volume=10 |issue=14 |pages=1677–94 |doi=10.2174/1381612043384655 |pmid=15134565}}</ref> In general, antioxidant systems either prevent these reactive species from being formed, or remove them, thus minimizing their damage.<ref name="Davies" /><ref name="Sies" />  Reactive oxygen species can have useful cellular functions, such as [[redox signaling]]. Thus, ideally, antioxidant systems do not remove oxidants entirely, but maintain them at some optimum concentration.<ref>{{Cite journal |vauthors=Rhee SG |date=June 2006 |title=Cell signaling. H2O2, a necessary evil for cell signaling |journal=Science |volume=312 |issue=5782 |pages=1882–3 |doi=10.1126/science.1130481 |pmid=16809515 |s2cid=83598498}}</ref>

Reactive oxygen species produced in cells include [[hydrogen peroxide]] (H<sub>2</sub>O<sub>2</sub>), [[hypochlorous acid]] (HClO), and [[free radical]]s such as the [[hydroxyl radical]] (·OH), and the [[superoxide|superoxide anion]] (O<sub>2</sub><sup>−</sup>).<ref name="emfafb">{{Cite journal |vauthors=Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J |year=2007 |title=Free radicals and antioxidants in normal physiological functions and human disease |journal=The International Journal of Biochemistry & Cell Biology |volume=39 |issue=1 |pages=44–84 |doi=10.1016/j.biocel.2006.07.001 |pmid=16978905}}</ref> The hydroxyl radical is particularly unstable and will react rapidly and non-specifically with most biological molecules. This species is produced from hydrogen peroxide in [[catalysis|metal-catalyzed]] redox reactions such as the [[Fenton reaction]].<ref name="ReferenceA">{{Cite journal |vauthors=Stohs SJ, Bagchi D |date=February 1995 |title=Oxidative mechanisms in the toxicity of metal ions |url=http://www8.umoncton.ca/umcm-gauthier_didier/bc6423/2SO/Strohs95.pdf |journal=Free Radical Biology & Medicine |type=Submitted manuscript |volume=18 |issue=2 |pages=321–36 |citeseerx=10.1.1.461.6417 |doi=10.1016/0891-5849(94)00159-H |pmid=7744317}}</ref> These oxidants can damage cells by starting chemical chain reactions such as [[lipid peroxidation]], or by oxidizing DNA or proteins.<ref name="Sies" /> Damage to DNA can cause [[mutation]]s and possibly [[cancer]], if not reversed by [[DNA repair]] mechanisms,<ref>{{Cite journal |vauthors=Nakabeppu Y, Sakumi K, Sakamoto K, Tsuchimoto D, Tsuzuki T, Nakatsu Y |date=April 2006 |title=Mutagenesis and carcinogenesis caused by the oxidation of nucleic acids |journal=Biological Chemistry |volume=387 |issue=4 |pages=373–9 |doi=10.1515/BC.2006.050 |pmid=16606334 |s2cid=20217256}}</ref><ref>{{Cite journal |vauthors=Valko M, Izakovic M, Mazur M, Rhodes CJ, Telser J |date=November 2004 |title=Role of oxygen radicals in DNA damage and cancer incidence |journal=Molecular and Cellular Biochemistry |volume=266 |issue=1–2 |pages=37–56 |doi=10.1023/B:MCBI.0000049134.69131.89 |pmid=15646026 |s2cid=207547763}}</ref> while damage to [[protein]]s causes enzyme inhibition, [[denaturation (biochemistry)|denaturation]], and [[proteasome|protein degradation]].<ref>{{Cite journal |vauthors=Stadtman ER |date=August 1992 |title=Protein oxidation and aging |url=https://zenodo.org/record/1230934 |journal=Science |volume=257 |issue=5074 |pages=1220–4 |bibcode=1992Sci...257.1220S |doi=10.1126/science.1355616 |pmid=1355616}}</ref>

The use of oxygen as part of the process for generating metabolic energy produces reactive oxygen species.<ref name="Raha">{{Cite journal |vauthors=Raha S, Robinson BH |date=October 2000 |title=Mitochondria, oxygen free radicals, disease and ageing |journal=Trends in Biochemical Sciences |volume=25 |issue=10 |pages=502–8 |doi=10.1016/S0968-0004(00)01674-1 |pmid=11050436}}</ref> In this process, the superoxide anion is produced as a [[by-product]] of several steps in the [[electron transport chain]].<ref>{{Cite journal |vauthors=Lenaz G |year=2001 |title=The mitochondrial production of reactive oxygen species: mechanisms and implications in human pathology |journal=IUBMB Life |volume=52 |issue=3–5 |pages=159–64 |doi=10.1080/15216540152845957 |pmid=11798028 |s2cid=45366190 |doi-access=free}}</ref> Particularly important is the reduction of [[coenzyme Q]] in [[complex III]], since a highly reactive free radical is formed as an intermediate (Q'''·'''<sup>−</sup>). This unstable intermediate can lead to electron "leakage", when electrons jump directly to oxygen and form the superoxide anion, instead of moving through the normal series of well-controlled reactions of the electron transport chain.<ref>{{Cite journal |vauthors=Finkel T, Holbrook NJ |date=November 2000 |title=Oxidants, oxidative stress and the biology of ageing |journal=Nature |volume=408 |issue=6809 |pages=239–47 |bibcode=2000Natur.408..239F |doi=10.1038/35041687 |pmid=11089981 |s2cid=2502238}}</ref> Peroxide is also produced from the oxidation of reduced [[flavoprotein]]s, such as [[complex I]].<ref>{{Cite journal |vauthors=Hirst J, King MS, Pryde KR |date=October 2008 |title=The production of reactive oxygen species by complex I |journal=Biochemical Society Transactions |volume=36 |issue=Pt 5 |pages=976–80 |doi=10.1042/BST0360976 |pmid=18793173}}</ref> However, although these enzymes can produce oxidants, the relative importance of the electron transfer chain to other processes that generate peroxide is unclear.<ref>{{Cite journal |vauthors=Seaver LC, Imlay JA |date=November 2004 |title=Are respiratory enzymes the primary sources of intracellular hydrogen peroxide? |journal=The Journal of Biological Chemistry |volume=279 |issue=47 |pages=48742–50 |doi=10.1074/jbc.M408754200 |pmid=15361522 |doi-access=free}}</ref><ref name="Pathways Ofoxidativedamage">{{Cite journal |vauthors=Imlay JA |year=2003 |title=Pathways of oxidative damage |journal=Annual Review of Microbiology |volume=57 |pages=395–418 |doi=10.1146/annurev.micro.57.030502.090938 |pmid=14527285}}</ref> In plants, [[algae]], and [[cyanobacteria]], reactive oxygen species are also produced during [[photosynthesis]],<ref>{{Cite journal |vauthors=Demmig-Adams B, Adams WW |date=December 2002 |title=Antioxidants in photosynthesis and human nutrition |journal=Science |volume=298 |issue=5601 |pages=2149–53 |bibcode=2002Sci...298.2149D |doi=10.1126/science.1078002 |pmid=12481128 |s2cid=27486669}}</ref> particularly under conditions of high [[irradiance|light intensity]].<ref>{{Cite journal |vauthors=Krieger-Liszkay A |date=January 2005 |title=Singlet oxygen production in photosynthesis |journal=Journal of Experimental Botany |volume=56 |issue=411 |pages=337–46 |citeseerx=10.1.1.327.9651 |doi=10.1093/jxb/erh237 |pmid=15310815}}</ref> This effect is partly offset by the involvement of [[carotenoid]]s in [[photoinhibition]], and in algae and cyanobacteria, by large amount of [[iodide]] and [[selenium]],<ref>{{Cite journal |vauthors=Kupper FC, Carpenter LJ, McFiggans GB, Palmer CJ, Waite TJ, Boneberg EM, Woitsch S, Weiller M, Abela R, Grolimund D, Potin P, Butler A, Luther GW, Kroneck PM, Meyer-Klaucke W, Feiters MC |year=2008 |title=Iodide accumulation provides kelp with an inorganic antioxidant impacting atmospheric chemistry |journal=[[Proceedings of the National Academy of Sciences]] |volume=105 |issue=19 |pages=6954–6958 |bibcode=2008PNAS..105.6954K |doi=10.1073/pnas.0709959105 |issn=0027-8424 |pmc=2383960 |pmid=18458346 |doi-access=free}}</ref> which involves these antioxidants reacting with over-reduced forms of the [[photosynthetic reaction centre]]s to prevent the production of reactive oxygen species.<ref>{{Cite journal |vauthors=Szabó I, Bergantino E, Giacometti GM |date=July 2005 |title=Light and oxygenic photosynthesis: energy dissipation as a protection mechanism against photo-oxidation |journal=EMBO Reports |volume=6 |issue=7 |pages=629–34 |doi=10.1038/sj.embor.7400460 |pmc=1369118 |pmid=15995679}}</ref><ref>{{Cite journal |vauthors=Kerfeld CA |date=October 2004 |title=Water-soluble carotenoid proteins of cyanobacteria |url=https://cloudfront.escholarship.org/dist/prd/content/qt3dm533x9/qt3dm533x9.pdf |journal=Archives of Biochemistry and Biophysics |type=Submitted manuscript |volume=430 |issue=1 |pages=2–9 |doi=10.1016/j.abb.2004.03.018 |pmid=15325905 |s2cid=25306222}}</ref>

=== Examples of bioactive antioxidant compounds ===
[[Physiology|Physiological]] antioxidants are classified into two broad divisions, depending on whether they are soluble in water ([[hydrophile|hydrophilic]]) or in lipids ([[Lipophilicity|lipophilic]]). In general, water-soluble antioxidants react with oxidants in the cell [[cytosol]] and the [[blood plasma]], while lipid-soluble antioxidants protect [[cell membrane]]s from [[lipid peroxidation]].<ref name="Sies" /> These compounds may be synthesized in the body or obtained from the diet.<ref name="Vertuani" /> The different antioxidants are present at a wide range of concentrations in [[Bodily fluid|body fluids]] and tissues, with some such as [[glutathione]] or [[ubiquinone]] mostly present within cells, while others such as [[uric acid]] are more systemically distributed (see table below). Some antioxidants are only found in a few organisms, and can be [[pathogen]]s or [[virulence factor]]s.<ref>{{Cite journal |vauthors=Miller RA, Britigan BE |date=January 1997 |title=Role of oxidants in microbial pathophysiology |journal=Clinical Microbiology Reviews |volume=10 |issue=1 |pages=1–18 |doi=10.1128/CMR.10.1.1 |pmc=172912 |pmid=8993856}}</ref>

The interactions between these different antioxidants may be [[synergy|synergistic]] and interdependent.<ref>{{Cite journal |vauthors=Chaudière J, Ferrari-Iliou R |year=1999 |title=Intracellular antioxidants: from chemical to biochemical mechanisms |journal=Food and Chemical Toxicology |volume=37 |issue=9–10 |pages=949–62 |doi=10.1016/S0278-6915(99)00090-3 |pmid=10541450}}</ref><ref>{{Cite journal |vauthors=Sies H |date=July 1993 |title=Strategies of antioxidant defense |journal=European Journal of Biochemistry |volume=215 |issue=2 |pages=213–9 |doi=10.1111/j.1432-1033.1993.tb18025.x |pmid=7688300 |doi-access=free}}</ref> The action of one antioxidant may therefore depend on the proper function of other members of the antioxidant system.<ref name="Vertuani" /> The amount of protection provided by any one antioxidant will also depend on its concentration, its reactivity towards the particular reactive oxygen species being considered, and the status of the antioxidants with which it interacts.<ref name="Vertuani" />

Some compounds contribute to antioxidant defense by [[chelation|chelating]] [[transition metal]]s and preventing them from catalyzing the production of free radicals in the cell. {{Better source needed|reason=The current source is insufficiently reliable ([[WP:NOTRS]]).|date=April 2025}}The ability to sequester iron for [[iron-binding proteins]], such as [[transferrin]] and [[ferritin]], is one such function.<ref name="Pathways Ofoxidativedamage" /> [[Selenium]] and [[zinc]] are commonly referred to as ''antioxidant minerals'', {{Better source needed|reason=The current source is insufficiently reliable ([[WP:NOTRS]]).|date=April 2025}}but these [[chemical element]]s have no antioxidant action themselves, but rather are required for the activity of antioxidant enzymes, such as [[glutathione reductase]] and [[superoxide dismutase]]. (See also [[selenium in biology]] and [[zinc in biology]].)

{| class="wikitable" style="margin-left: auto; margin-right: auto; text-align:center;"
|-
!Antioxidant
!Solubility
!Concentration in human serum ({{abbr|μM|micromolar}})
!Concentration in liver tissue ({{abbr|μmol/kg|micromoles per kilogram}})
|-
| [[Ascorbic acid]] ([[vitamin C]])
| Water
| 50–60<ref>{{Cite journal |vauthors=Khaw KT, Woodhouse P |date=June 1995 |title=Interrelation of vitamin C, infection, haemostatic factors, and cardiovascular disease |journal=BMJ |volume=310 |issue=6994 |pages=1559–63 |doi=10.1136/bmj.310.6994.1559 |pmc=2549940 |pmid=7787643}}</ref>
| 260 (human)<ref name="Evelson">{{Cite journal |vauthors=Evelson P, Travacio M, Repetto M, Escobar J, Llesuy S, Lissi EA |date=April 2001 |title=Evaluation of total reactive antioxidant potential (TRAP) of tissue homogenates and their cytosols |journal=Archives of Biochemistry and Biophysics |volume=388 |issue=2 |pages=261–6 |doi=10.1006/abbi.2001.2292 |pmid=11368163}}</ref>
|-
| [[Glutathione]]
| Water
| 4<ref>{{Cite journal |vauthors=Morrison JA, Jacobsen DW, Sprecher DL, Robinson K, Khoury P, Daniels SR |date=November 1999 |title=Serum glutathione in adolescent males predicts parental coronary heart disease |journal=Circulation |volume=100 |issue=22 |pages=2244–7 |doi=10.1161/01.CIR.100.22.2244 |pmid=10577998 |doi-access=free}}</ref>
| 6,400 (human)<ref name="Evelson" />
|-
| [[Lipoic acid]]
| Water
| 0.1–0.7<ref>{{Cite journal |vauthors=Teichert J, Preiss R |date=November 1992 |title=HPLC-methods for determination of lipoic acid and its reduced form in human plasma |journal=International Journal of Clinical Pharmacology, Therapy, and Toxicology |volume=30 |issue=11 |pages=511–2 |pmid=1490813}}</ref>
| 4–5 (rat)<ref>{{Cite journal |vauthors=Akiba S, Matsugo S, Packer L, Konishi T |date=May 1998 |title=Assay of protein-bound lipoic acid in tissues by a new enzymatic method |journal=Analytical Biochemistry |volume=258 |issue=2 |pages=299–304 |doi=10.1006/abio.1998.2615 |pmid=9570844}}</ref>
|-
| [[Uric acid]]
| Water
| 200–400<ref name="Glantzounis">{{Cite journal |vauthors=Glantzounis GK, Tsimoyiannis EC, Kappas AM, Galaris DA |year=2005 |title=Uric acid and oxidative stress |journal=Current Pharmaceutical Design |volume=11 |issue=32 |pages=4145–51 |doi=10.2174/138161205774913255 |pmid=16375736}}</ref>
| 1,600 (human)<ref name="Evelson" />
|-
| [[Carotene]]s
| Lipid
| [[carotene|β-carotene]]: 0.5–1<ref>{{Cite journal |vauthors=El-Sohemy A, Baylin A, Kabagambe E, Ascherio A, Spiegelman D, Campos H |date=July 2002 |title=Individual carotenoid concentrations in adipose tissue and plasma as biomarkers of dietary intake |journal=The American Journal of Clinical Nutrition |volume=76 |issue=1 |pages=172–9 |doi=10.1093/ajcn/76.1.172 |pmid=12081831 |doi-access=free}}</ref>
[[retinol]] (vitamin A): 1–3<ref name="Sowell">{{Cite journal |vauthors=Sowell AL, Huff DL, Yeager PR, Caudill SP, Gunter EW |date=March 1994 |title=Retinol, alpha-tocopherol, lutein/zeaxanthin, beta-cryptoxanthin, lycopene, alpha-carotene, trans-beta-carotene, and four retinyl esters in serum determined simultaneously by reversed-phase HPLC with multiwavelength detection |journal=Clinical Chemistry |volume=40 |issue=3 |pages=411–6 |doi=10.1093/clinchem/40.3.411 |pmid=8131277 |doi-access=free}}</ref>
| 5 (human, total carotenoids)<ref>{{Cite journal |vauthors=Stahl W, Schwarz W, Sundquist AR, Sies H |date=April 1992 |title=cis-trans isomers of lycopene and beta-carotene in human serum and tissues |journal=Archives of Biochemistry and Biophysics |volume=294 |issue=1 |pages=173–7 |doi=10.1016/0003-9861(92)90153-N |pmid=1550343}}</ref>
|-
| [[tocopherol|α-Tocopherol]] (vitamin E)
| Lipid
| 10–40<ref name="Sowell" />
| 50 (human)<ref name="Evelson" />
|-
| [[Coenzyme Q|Ubiquinol]] (coenzyme Q)
| Lipid
| 5<ref>{{Cite journal |vauthors=Zita C, Overvad K, Mortensen SA, Sindberg CD, Moesgaard S, Hunter DA |year=2003 |title=Serum coenzyme Q10 concentrations in healthy men supplemented with 30 mg or 100 mg coenzyme Q10 for two months in a randomised controlled study |journal=BioFactors |volume=18 |issue=1–4 |pages=185–93 |doi=10.1002/biof.5520180221 |pmid=14695934 |s2cid=19895215}}</ref>
| 200 (human)<ref name="Turunen">{{Cite journal |vauthors=Turunen M, Olsson J, Dallner G |date=January 2004 |title=Metabolism and function of coenzyme Q |journal=Biochimica et Biophysica Acta (BBA) - Biomembranes |volume=1660 |issue=1–2 |pages=171–99 |doi=10.1016/j.bbamem.2003.11.012 |pmid=14757233 |doi-access=free}}</ref>
|}

==== Uric acid ====
[[Uric acid]] has the highest concentration of any blood antioxidant<ref name="Glantzounis" /> and provides over half of the total antioxidant capacity of human serum.<ref>{{Cite journal |vauthors=Becker BF |date=June 1993 |title=Towards the physiological function of uric acid |journal=Free Radical Biology & Medicine |volume=14 |issue=6 |pages=615–31 |doi=10.1016/0891-5849(93)90143-I |pmid=8325534}}</ref> Uric acid's antioxidant activities are also complex, given that it does not react with some oxidants, such as [[superoxide]], but does act against [[peroxynitrite]],<ref name="Sautin2008">{{Cite journal |vauthors=Sautin YY, Johnson RJ |date=June 2008 |title=Uric acid: the oxidant-antioxidant paradox |journal=Nucleosides, Nucleotides & Nucleic Acids |volume=27 |issue=6 |pages=608–19 |doi=10.1080/15257770802138558 |pmc=2895915 |pmid=18600514}}</ref> [[peroxide]]s, and [[hypochlorous acid]].<ref name="Enomoto2005">{{Cite journal |vauthors=Enomoto A, Endou H |date=September 2005 |title=Roles of organic anion transporters (OATs) and a urate transporter (URAT1) in the pathophysiology of human disease |journal=Clinical and Experimental Nephrology |volume=9 |issue=3 |pages=195–205 |doi=10.1007/s10157-005-0368-5 |pmid=16189627 |s2cid=6145651}}</ref> Concerns over elevated UA's contribution to [[gout]] must be considered one of many risk factors.<ref name="Eggebeen2007">{{Cite journal |vauthors=Eggebeen AT |date=September 2007 |title=Gout: an update |url=http://www.aafp.org/link_out?pmid=17910294 |journal=American Family Physician |volume=76 |issue=6 |pages=801–8 |pmid=17910294}}</ref> By itself, UA-related risk of gout at high levels (415–530 μmol/L) is only 0.5% per year with an increase to 4.5% per year at UA [[supersaturation|supersaturation levels]] (535+ μmol/L).<ref name="Campion1987">{{Cite journal |vauthors=Campion EW, Glynn RJ, DeLabry LO |date=March 1987 |title=Asymptomatic hyperuricemia. Risks and consequences in the Normative Aging Study |journal=The American Journal of Medicine |volume=82 |issue=3 |pages=421–6 |doi=10.1016/0002-9343(87)90441-4 |pmid=3826098}}</ref> Many of these aforementioned studies determined UA's antioxidant actions within normal physiological levels,<ref name="Baillie2007">{{Cite journal |vauthors=Baillie JK, Bates MG, Thompson AA, Waring WS, Partridge RW, Schnopp MF, Simpson A, Gulliver-Sloan F, Maxwell SR, Webb DJ |date=May 2007 |title=Endogenous urate production augments plasma antioxidant capacity in healthy lowland subjects exposed to high altitude |journal=Chest |volume=131 |issue=5 |pages=1473–8 |doi=10.1378/chest.06-2235 |pmid=17494796}}</ref><ref name="Sautin2008" /> and some found antioxidant activity at levels as high as 285 μmol/L.<ref name="Nazarewicz2007">{{Cite journal |vauthors=Nazarewicz RR, Ziolkowski W, Vaccaro PS, Ghafourifar P |date=December 2007 |title=Effect of short-term ketogenic diet on redox status of human blood |journal=Rejuvenation Research |volume=10 |issue=4 |pages=435–40 |doi=10.1089/rej.2007.0540 |pmid=17663642}}</ref>

==== Vitamin C ====
[[Ascorbic acid]] or [[vitamin C]], an oxidation-reduction ([[redox]]) [[catalyst]] found in both animals and plants,<ref name="lpi2018">{{Cite web |date=1 July 2018 |title=Vitamin C |url=http://lpi.oregonstate.edu/mic/vitamins/vitamin-C |access-date=19 June 2019 |publisher=Micronutrient Information Center, Linus Pauling Institute, Oregon State University, Corvallis, OR}}</ref> can reduce, and thereby neutralize, reactive oxygen species such as hydrogen peroxide.<ref name="lpi2018" /><ref>{{Cite journal |vauthors=Padayatty SJ, Katz A, Wang Y, Eck P, Kwon O, Lee JH, Chen S, Corpe C, Dutta A, Dutta SK, Levine M |date=February 2003 |title=Vitamin C as an antioxidant: evaluation of its role in disease prevention |url=http://www.jacn.org/cgi/pmidlookup?view=long&pmid=12569111 |journal=Journal of the American College of Nutrition |volume=22 |issue=1 |pages=18–35 |doi=10.1080/07315724.2003.10719272 |pmid=12569111 |s2cid=21196776}}</ref> In addition to its direct antioxidant effects, ascorbic acid is also a [[substrate (biochemistry)|substrate]] for the redox enzyme [[ascorbate peroxidase]], a function that is used in stress resistance in plants.<ref>{{Cite journal |vauthors=Shigeoka S, Ishikawa T, Tamoi M, Miyagawa Y, Takeda T, Yabuta Y, Yoshimura K |date=May 2002 |title=Regulation and function of ascorbate peroxidase isoenzymes |journal=Journal of Experimental Botany |volume=53 |issue=372 |pages=1305–19 |doi=10.1093/jexbot/53.372.1305 |pmid=11997377 |doi-access=free}}</ref> Ascorbic acid is present at high levels in all parts of plants and can reach concentrations of 20&nbsp;[[millimolar]] in [[chloroplast]]s.<ref>{{Cite journal |vauthors=Smirnoff N, Wheeler GL |year=2000 |title=Ascorbic acid in plants: biosynthesis and function |journal=Critical Reviews in Biochemistry and Molecular Biology |volume=35 |issue=4 |pages=291–314 |doi=10.1080/10409230008984166 |pmid=11005203 |s2cid=85060539}}</ref>

==== Glutathione ====
[[Image:Lipid peroxidation.svg|thumb|right|class=skin-invert-image|The [[Radical (chemistry)|free radical]] mechanism of lipid peroxidation]]

[[Glutathione]] has antioxidant properties since the [[thiol]] group in its [[cysteine]] [[moiety (chemistry)|moiety]] is a reducing agent and can be reversibly oxidized and reduced. In cells, glutathione is maintained in the reduced form by the enzyme [[glutathione reductase]] and in turn reduces other metabolites and enzyme systems, such as ascorbate in the [[glutathione-ascorbate cycle]], [[glutathione peroxidase]]s and [[glutaredoxin]]s, as well as reacting directly with oxidants.<ref name="MeisterA">{{Cite journal |vauthors=Meister A |date=April 1994 |title=Glutathione-ascorbic acid antioxidant system in animals |url=https://www.jbc.org/article/S0021-9258(17)36891-6/pdf |journal=The Journal of Biological Chemistry |volume=269 |issue=13 |pages=9397–400 |doi=10.1016/S0021-9258(17)36891-6 |pmid=8144521 |doi-access=free}}</ref> Due to its high concentration and its central role in maintaining the cell's redox state, glutathione is one of the most important cellular antioxidants.<ref name="MeisterB">{{Cite journal |vauthors=Meister A, Anderson ME |year=1983 |title=Glutathione |journal=Annual Review of Biochemistry |volume=52 |pages=711–60 |doi=10.1146/annurev.bi.52.070183.003431 |pmid=6137189}}</ref> In some organisms glutathione is replaced by other thiols, such as by [[mycothiol]] in the [[Actinomycete]]s, [[bacillithiol]] in some [[gram-positive bacteria]],<ref name="pmid20308541">{{Cite journal |vauthors=Gaballa A, Newton GL, Antelmann H, Parsonage D, Upton H, Rawat M, Claiborne A, Fahey RC, Helmann JD |date=April 2010 |title=Biosynthesis and functions of bacillithiol, a major low-molecular-weight thiol in Bacilli |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=107 |issue=14 |pages=6482–6 |bibcode=2010PNAS..107.6482G |doi=10.1073/pnas.1000928107 |pmc=2851989 |pmid=20308541 |doi-access=free}}</ref><ref name="Newton">{{Cite journal |vauthors=Newton GL, Rawat M, La Clair JJ, Jothivasan VK, Budiarto T, Hamilton CJ, Claiborne A, Helmann JD, Fahey RC |date=September 2009 |title=Bacillithiol is an antioxidant thiol produced in Bacilli |journal=Nature Chemical Biology |volume=5 |issue=9 |pages=625–627 |doi=10.1038/nchembio.189 |pmc=3510479 |pmid=19578333}}</ref> or by [[trypanothione]] in the [[Kinetoplastida|Kinetoplastids]].<ref>{{Cite journal |vauthors=Fahey RC |year=2001 |title=Novel thiols of prokaryotes |journal=Annual Review of Microbiology |volume=55 |pages=333–56 |doi=10.1146/annurev.micro.55.1.333 |pmid=11544359}}</ref><ref>{{Cite journal |vauthors=Fairlamb AH, Cerami A |year=1992 |title=Metabolism and functions of trypanothione in the Kinetoplastida |journal=Annual Review of Microbiology |volume=46 |pages=695–729 |doi=10.1146/annurev.mi.46.100192.003403 |pmid=1444271}}</ref>

==== Vitamin E ====
[[Vitamin E]] is the collective name for a set of eight related [[tocopherol]]s and [[tocotrienol]]s, which are [[fat-soluble]] vitamins with antioxidant properties.<ref name="Herrera">{{Cite journal |author-link2=Coral Barbas |vauthors=Herrera E, Barbas C |date=March 2001 |title=Vitamin E: action, metabolism and perspectives |journal=Journal of Physiology and Biochemistry |volume=57 |issue=2 |pages=43–56 |doi=10.1007/BF03179812 |pmid=11579997 |s2cid=7272312 |hdl-access=free |hdl=10637/720}}</ref><ref>{{Cite journal |vauthors=Packer L, Weber SU, Rimbach G |date=February 2001 |title=Molecular aspects of alpha-tocotrienol antioxidant action and cell signalling |journal=The Journal of Nutrition |volume=131 |issue=2 |pages=369S–73S |doi=10.1093/jn/131.2.369S |pmid=11160563 |doi-access=free}}</ref> Of these, α-tocopherol has been most studied as it has the highest [[bioavailability]], with the body preferentially absorbing and metabolising this form.<ref name="Brigelius">{{Cite journal |vauthors=Brigelius-Flohé R, Traber MG |date=July 1999 |title=Vitamin E: function and metabolism |journal=FASEB Journal |volume=13 |issue=10 |pages=1145–55 |citeseerx=10.1.1.337.5276 |doi=10.1096/fasebj.13.10.1145 |pmid=10385606 |s2cid=7031925 |doi-access=free}}</ref>

It has been claimed{{by whom|date=September 2024}} that the α-tocopherol form is the most important lipid-soluble antioxidant, and that it protects membranes from oxidation by reacting with lipid radicals produced in the lipid peroxidation chain reaction.<ref name="Herrera" /><ref>{{Cite journal |vauthors=Traber MG, Atkinson J |date=July 2007 |title=Vitamin E, antioxidant and nothing more |journal=Free Radical Biology & Medicine |volume=43 |issue=1 |pages=4–15 |doi=10.1016/j.freeradbiomed.2007.03.024 |pmc=2040110 |pmid=17561088}}</ref> This removes the free radical intermediates and prevents the propagation reaction from continuing. This reaction produces oxidised α-tocopheroxyl radicals that can be recycled back to the active reduced form through reduction by other antioxidants, such as ascorbate, retinol or ubiquinol.<ref>{{Cite journal |vauthors=Wang X, Quinn PJ |date=July 1999 |title=Vitamin E and its function in membranes |journal=Progress in Lipid Research |volume=38 |issue=4 |pages=309–36 |doi=10.1016/S0163-7827(99)00008-9 |pmid=10793887}}</ref> This is in line with findings showing that α-tocopherol, but not water-soluble antioxidants, efficiently protects glutathione peroxidase 4 ([[GPX4]])-deficient cells from cell death.<ref>{{Cite journal |vauthors=Seiler A, Schneider M, Förster H, Roth S, Wirth EK, Culmsee C, Plesnila N, Kremmer E, Rådmark O, Wurst W, Bornkamm GW, Schweizer U, Conrad M |date=September 2008 |title=Glutathione peroxidase 4 senses and translates oxidative stress into 12/15-lipoxygenase dependent- and AIF-mediated cell death |journal=Cell Metabolism |volume=8 |issue=3 |pages=237–48 |doi=10.1016/j.cmet.2008.07.005 |pmid=18762024 |doi-access=free}}</ref> GPx4 is the only known enzyme that efficiently reduces lipid-hydroperoxides within biological membranes.{{citation needed|date=November 2024}}

However, the roles and importance of the various forms of vitamin E are presently unclear,<ref>{{Cite journal |vauthors=Brigelius-Flohé R, Davies KJ |date=July 2007 |title=Is vitamin E an antioxidant, a regulator of signal transduction and gene expression, or a 'junk' food? Comments on the two accompanying papers: "Molecular mechanism of alpha-tocopherol action" by A. Azzi and "Vitamin E, antioxidant and nothing more" by M. Traber and J. Atkinson |journal=Free Radical Biology & Medicine |volume=43 |issue=1 |pages=2–3 |doi=10.1016/j.freeradbiomed.2007.05.016 |pmid=17561087}}</ref><ref>{{Cite journal |vauthors=Atkinson J, Epand RF, Epand RM |date=March 2008 |title=Tocopherols and tocotrienols in membranes: a critical review |journal=Free Radical Biology & Medicine |volume=44 |issue=5 |pages=739–64 |doi=10.1016/j.freeradbiomed.2007.11.010 |pmid=18160049}}</ref> and it has even been suggested that the most important function of α-tocopherol is as a [[cell signaling|signaling molecule]], with this molecule having no significant role in antioxidant metabolism.<ref name="Azzi">{{Cite journal |vauthors=Azzi A |date=July 2007 |title=Molecular mechanism of alpha-tocopherol action |journal=Free Radical Biology & Medicine |volume=43 |issue=1 |pages=16–21 |doi=10.1016/j.freeradbiomed.2007.03.013 |pmid=17561089}}</ref><ref>{{Cite journal |vauthors=Zingg JM, Azzi A |date=May 2004 |title=Non-antioxidant activities of vitamin E |url=http://www.benthamdirect.org/pages/content.php?CMC/2004/00000011/00000009/0005C.SGM |url-status=dead |journal=Current Medicinal Chemistry |volume=11 |issue=9 |pages=1113–33 |doi=10.2174/0929867043365332 |pmid=15134510 |archive-url=https://web.archive.org/web/20111006103310/http://www.benthamdirect.org/pages/content.php?CMC%2F2004%2F00000011%2F00000009%2F0005C.SGM |archive-date=6 October 2011}}</ref> The functions of the other forms of vitamin E are even less well understood, although γ-tocopherol is a [[nucleophile]] that may react with [[electrophile|electrophilic]] mutagens,<ref name="Brigelius" /> and tocotrienols may be important in protecting [[neuron]]s from damage.<ref>{{Cite journal |vauthors=Sen CK, Khanna S, Roy S |date=March 2006 |title=Tocotrienols: Vitamin E beyond tocopherols |journal=Life Sciences |volume=78 |issue=18 |pages=2088–98 |doi=10.1016/j.lfs.2005.12.001 |pmc=1790869 |pmid=16458936}}</ref>

=== Pro-oxidant activities ===
{{further|Pro-oxidant}}

Antioxidants that are reducing agents can also act as pro-oxidants. For example, vitamin C has antioxidant activity when it reduces oxidizing substances such as hydrogen peroxide;<ref>{{Cite journal |vauthors=Duarte TL, Lunec J |date=July 2005 |title=Review: When is an antioxidant not an antioxidant? A review of novel actions and reactions of vitamin C |journal=Free Radical Research |volume=39 |issue=7 |pages=671–86 |doi=10.1080/10715760500104025 |pmid=16036346 |s2cid=39962659}}</ref> however, it will also reduce metal ions such as iron and copper<ref name="ReferenceB">{{Cite journal |last1=Shen |first1=Jiaqi |last2=Griffiths |first2=Paul T. |last3=Campbell |first3=Steven J. |last4=Utinger |first4=Battist |last5=Kalberer |first5=Markus |last6=Paulson |first6=Suzanne E. |date=2021-04-01 |title=Ascorbate oxidation by iron, copper and reactive oxygen species: review, model development, and derivation of key rate constants |journal=Scientific Reports |language=en |volume=11 |issue=1 |pages=7417 |bibcode=2021NatSR..11.7417S |doi=10.1038/s41598-021-86477-8 |issn=2045-2322 |pmc=8016884 |pmid=33795736}}</ref> that generate free radicals through the [[Fenton's reagent|Fenton reaction]].<ref name="ReferenceA" /><ref name="Carr">{{Cite journal |vauthors=Carr A, Frei B |date=June 1999 |title=Does vitamin C act as a pro-oxidant under physiological conditions? |journal=FASEB Journal |volume=13 |issue=9 |pages=1007–24 |doi=10.1096/fasebj.13.9.1007 |pmid=10336883 |s2cid=15426564 |doi-access=free}}</ref> While ascorbic acid is effective antioxidant, it can also oxidatively change the flavor and color of food. With the presence of transition metals, there are low concentrations of ascorbic acid that can act as a radical scavenger in the Fenton reaction.<ref name="ReferenceB" />

:2 Fe<sup>3+</sup> + Ascorbate → 2 Fe<sup>2+</sup> + Dehydroascorbate

:2 Fe<sup>2+</sup> + 2 H<sub>2</sub>O<sub>2</sub> → 2 Fe<sup>3+</sup> + 2 OH'''·''' + 2 OH<sup>−</sup>

The relative importance of the antioxidant and pro-oxidant activities of antioxidants is an area of current research, but vitamin C, which exerts its effects as a vitamin by oxidizing polypeptides, appears to have a mostly antioxidant action in the human body.<ref name="Carr" />

=== Enzyme systems ===
{{Image frame|caption=Enzymatic pathway&nbsp;for detoxification of reactive oxygen species
|content=<chem>
\underset{Oxygen}{O2} -> \underset{Superoxide}{*O2^-} ->[\ce{Superoxide \atop dismutase}] \underset{Hydrogen \atop peroxide}{H2O2} ->[\ce{Peroxidases \atop catalase}] \underset{Water}{H2O}
</chem>}}
As with the chemical antioxidants, cells are protected against oxidative stress by an interacting network of antioxidant enzymes.<ref name="Davies" /><ref name="Sies" /> Here, the superoxide released by processes such as [[oxidative phosphorylation]] is first converted to hydrogen peroxide and then further reduced to give water. This detoxification pathway is the result of multiple enzymes, with superoxide dismutases catalysing the first step and then catalases and various peroxidases removing hydrogen peroxide. As with antioxidant metabolites, the contributions of these enzymes to antioxidant defenses can be hard to separate from one another, but the generation of [[Genetically modified organism|transgenic mice]] lacking just one antioxidant enzyme can be informative.<ref name="Magnenat">{{Cite journal |vauthors=Ho YS, Magnenat JL, Gargano M, Cao J |date=October 1998 |title=The nature of antioxidant defense mechanisms: a lesson from transgenic studies |journal=Environmental Health Perspectives |volume=106 |issue=Suppl 5 |pages=1219–28 |doi=10.2307/3433989 |jstor=3433989 |pmc=1533365 |pmid=9788901}}</ref>

==== 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>

==== Thioredoxin and glutathione systems ====
The [[thioredoxin]] system contains the 12-k[[atomic mass unit|Da]] protein thioredoxin and its companion [[thioredoxin reductase]].<ref>{{Cite journal |vauthors=Nordberg J, Arnér ES |date=December 2001 |title=Reactive oxygen species, antioxidants, and the mammalian thioredoxin system |journal=Free Radical Biology & Medicine |volume=31 |issue=11 |pages=1287–312 |doi=10.1016/S0891-5849(01)00724-9 |pmid=11728801}}</ref> Proteins related to thioredoxin are present in all sequenced organisms. Plants, such as ''[[Arabidopsis thaliana]],'' have a particularly great diversity of isoforms.<ref>{{Cite journal |vauthors=Vieira Dos Santos C, Rey P |date=July 2006 |title=Plant thioredoxins are key actors in the oxidative stress response |journal=Trends in Plant Science |volume=11 |issue=7 |pages=329–34 |bibcode=2006TPS....11..329V |doi=10.1016/j.tplants.2006.05.005 |pmid=16782394}}</ref> The active site of thioredoxin consists of two [[vicinal (chemistry)|neighboring]] cysteines, as part of a highly conserved CXXC [[sequence motif|motif]], that can cycle between an active dithiol form (reduced) and an oxidized [[disulfide]] form. In its active state, thioredoxin acts as an efficient reducing agent, scavenging reactive oxygen species and maintaining other proteins in their reduced state.<ref>{{Cite journal |vauthors=Arnér ES, Holmgren A |date=October 2000 |title=Physiological functions of thioredoxin and thioredoxin reductase |journal=European Journal of Biochemistry |volume=267 |issue=20 |pages=6102–9 |doi=10.1046/j.1432-1327.2000.01701.x |pmid=11012661 |doi-access=free}}</ref> After being oxidized, the active thioredoxin is regenerated by the action of thioredoxin reductase, using [[NADPH]] as an [[electron donor]].<ref>{{Cite journal |vauthors=Mustacich D, Powis G |date=February 2000 |title=Thioredoxin reductase |journal=The Biochemical Journal |volume=346 |issue=1 |pages=1–8 |doi=10.1042/0264-6021:3460001 |pmc=1220815 |pmid=10657232}}</ref>

The [[glutathione]] system includes glutathione, [[glutathione reductase]], [[glutathione peroxidase]]s, and [[glutathione S-transferase|glutathione ''S''-transferases]].<ref name="MeisterB" /> This system is found in animals, plants and microorganisms.<ref name="MeisterB" /><ref>{{Cite journal |vauthors=Creissen G, Broadbent P, Stevens R, Wellburn AR, Mullineaux P |date=May 1996 |title=Manipulation of glutathione metabolism in transgenic plants |journal=Biochemical Society Transactions |volume=24 |issue=2 |pages=465–9 |doi=10.1042/bst0240465 |pmid=8736785}}</ref> Glutathione peroxidase is an enzyme containing four [[selenium]]-[[cofactor (biochemistry)|cofactors]] that catalyzes the breakdown of hydrogen peroxide and organic hydroperoxides. There are at least four different glutathione peroxidase [[isozyme]]s in animals.<ref>{{Cite journal |vauthors=Brigelius-Flohé R |date=November 1999 |title=Tissue-specific functions of individual glutathione peroxidases |journal=Free Radical Biology & Medicine |volume=27 |issue=9–10 |pages=951–65 |doi=10.1016/S0891-5849(99)00173-2 |pmid=10569628}}</ref> Glutathione peroxidase 1 is the most abundant and is a very efficient scavenger of hydrogen peroxide, while glutathione peroxidase 4 is most active with lipid hydroperoxides. Surprisingly, glutathione peroxidase 1 is dispensable, as mice lacking this enzyme have normal lifespans,<ref>{{Cite journal |vauthors=Ho YS, Magnenat JL, Bronson RT, Cao J, Gargano M, Sugawara M, Funk CD |date=June 1997 |title=Mice deficient in cellular glutathione peroxidase develop normally and show no increased sensitivity to hyperoxia |journal=The Journal of Biological Chemistry |volume=272 |issue=26 |pages=16644–51 |doi=10.1074/jbc.272.26.16644 |pmid=9195979 |doi-access=free}}</ref> but they are hypersensitive to induced oxidative stress.<ref>{{Cite journal |vauthors=de Haan JB, Bladier C, Griffiths P, Kelner M, O'Shea RD, Cheung NS, Bronson RT, Silvestro MJ, Wild S, Zheng SS, Beart PM, Hertzog PJ, Kola I |date=August 1998 |title=Mice with a homozygous null mutation for the most abundant glutathione peroxidase, Gpx1, show increased susceptibility to the oxidative stress-inducing agents paraquat and hydrogen peroxide |journal=The Journal of Biological Chemistry |volume=273 |issue=35 |pages=22528–36 |doi=10.1074/jbc.273.35.22528 |pmid=9712879 |doi-access=free |hdl-access=free |hdl=10536/DRO/DU:30101410}}</ref> In addition, the glutathione ''S''-transferases show high activity with lipid peroxides.<ref>{{Cite journal |vauthors=Sharma R, Yang Y, Sharma A, Awasthi S, Awasthi YC |date=April 2004 |title=Antioxidant role of glutathione S-transferases: protection against oxidant toxicity and regulation of stress-mediated apoptosis |journal=Antioxidants & Redox Signaling |volume=6 |issue=2 |pages=289–300 |doi=10.1089/152308604322899350 |pmid=15025930}}</ref> These enzymes are at particularly high levels in the liver and also serve in [[detoxification]] metabolism.<ref>{{Cite journal |vauthors=Hayes JD, Flanagan JU, Jowsey IR |year=2005 |title=Glutathione transferases |journal=Annual Review of Pharmacology and Toxicology |volume=45 |pages=51–88 |doi=10.1146/annurev.pharmtox.45.120403.095857 |pmid=15822171}}</ref>