Editing Antioxidant (section)

=== 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>