Editing Glutathione (section)

==Roles==

===Antioxidant===
GSH protects cells by neutralising (reducing) [[reactive oxygen species]].<ref name=Brownlee>{{cite journal|title=The pathobiology of diabetic complications: A unifying mechanism|journal=Diabetes|year=2005|volume=54|issue=6|pages=1615–25|doi=10.2337/diabetes.54.6.1615|pmid=15919781|author=Michael Brownlee|doi-access=free}}</ref><ref name=Wu>{{cite journal |author=Guoyao Wu |author2=Yun-Zhong Fang |author3=Sheng Yang |author4=Joanne R. Lupton |author5=Nancy D. Turner |title=Glutathione Metabolism and its Implications for Health|journal=Journal of Nutrition|year=2004|volume=134|issue=3|pages=489–492|doi=10.1093/jn/134.3.489|pmid=14988435|doi-access=free}}</ref> This conversion is illustrated by the reduction of peroxides:
:2 GSH  +  R<sub>2</sub>O<sub>2</sub> →  GSSG  +  2 ROH {{pad|2em}}(R = H, alkyl)
and with free radicals:
:GSH  +  R<sup>•</sup> →  {{sfrac|1|2}} GSSG  +  RH

===Regulation===
Aside from deactivating radicals and reactive oxidants, glutathione participates in thiol protection and redox regulation of cellular thiol proteins under oxidative stress by protein ''S''-glutathionylation, a redox-regulated post-translational thiol modification.  The general reaction involves formation of an unsymmetrical disulfide from the protectable protein (RSH) and GSH:<ref>{{cite journal|title=Protein ''S''-glutathionylation: a regulatory device from bacteria to humans |author=Dalle-Donne, Isabella |author2=Rossi, Ranieri |author3=Colombo, Graziano |author4=Giustarini, Daniela |author5=Milzani, Aldo |journal=Trends in Biochemical Sciences|year=2009|volume=34|issue=2|pages=85–96|doi=10.1016/j.tibs.2008.11.002|pmid=19135374}}</ref>
:RSH  +  GSH  + [O]  →  GSSR   +  H<sub>2</sub>O

Glutathione is also employed for the [[detoxification]] of [[methylglyoxal]] and [[formaldehyde]], toxic metabolites produced under oxidative stress. This detoxification reaction is carried out by the [[glyoxalase system]]. [[Glyoxalase I]] (EC 4.4.1.5) catalyzes the conversion of methylglyoxal and reduced glutathione to ''S''-<small>D</small>-lactoylglutathione. [[Glyoxalase II]] (EC 3.1.2.6) catalyzes the hydrolysis of ''S''-<small>D</small>-lactoylglutathione to glutathione and [[lactic acid|<small>D</small>-lactic acid]].

It maintains exogenous antioxidants such as [[vitamin C|vitamins C]] and [[Vitamin E|E]] in their reduced (active) states.<ref>{{cite journal | vauthors = Dringen R | title = Metabolism and functions of glutathione in brain | journal = Progress in Neurobiology | volume = 62 | issue = 6 | pages = 649–671 | date = December 2000 | pmid = 10880854 | doi = 10.1016/s0301-0082(99)00060-x | s2cid = 452394 }}</ref><ref>{{cite journal | vauthors = Scholz RW, Graham KS, Gumpricht E, Reddy CC | year = 1989 | title = Mechanism of interaction of vitamin E and glutathione in the protection against membrane lipid peroxidation | journal = Annals of the New York Academy of Sciences | volume = 570 | issue = 1| pages = 514–7 | doi=10.1111/j.1749-6632.1989.tb14973.x| bibcode = 1989NYASA.570..514S | s2cid = 85414084 }}</ref><ref>{{cite journal | vauthors = Hughes RE | name-list-style = vanc | year = 1964 | title = Reduction of dehydroascorbic acid by animal tissues | journal = Nature | volume = 203 | issue = 4949| pages = 1068–9 | doi=10.1038/2031068a0 | pmid = 14223080 | bibcode = 1964Natur.203.1068H | s2cid = 4273230 }}</ref>

===Metabolism===
Among the many metabolic processes in which it participates, glutathione is required for the biosynthesis of [[leukotriene]]s and [[prostaglandin]]s. It plays a role in the storage of cysteine. Glutathione enhances the function of [[citrulline]] as part of the [[nitric oxide]] cycle.<ref>{{cite journal | vauthors = Ha SB, Smith AP, Howden R, Dietrich WM, Bugg S, O'Connell MJ, Goldsbrough PB, Cobbett CS | title = Phytochelatin synthase genes from Arabidopsis and the yeast ''Schizosaccharomyces pombe'' | journal = The Plant Cell | volume = 11 | issue = 6 | pages = 1153–64 | date = June 1999 | pmid = 10368185 | pmc = 144235 | doi = 10.1105/tpc.11.6.1153 | jstor = 3870806 }}</ref> It is a [[cofactor (biochemistry)|cofactor]] and acts on [[glutathione peroxidase]].<ref name="Grant_2001">{{cite journal | vauthors = Grant CM | title = Role of the glutathione/glutaredoxin and thioredoxin systems in yeast growth and response to stress conditions | journal = Molecular Microbiology | volume = 39 | issue = 3 | pages = 533–541 | year = 2001 | pmid = 11169096 | doi = 10.1046/j.1365-2958.2001.02283.x | s2cid = 6467802 | doi-access = free }}</ref> Glutathione is used to produce S-sulfanylglutathione, which is part of [[hydrogen sulfide]] metabolism.<ref>{{cite journal |last1=Melideo |first1=SL |last2=Jackson |first2=MR |last3=Jorns |first3=MS |title=Biosynthesis of a central intermediate in hydrogen sulfide metabolism by a novel human sulfurtransferase and its yeast ortholog. |journal=Biochemistry |date=22 July 2014 |volume=53 |issue=28 |pages=4739–53 |doi=10.1021/bi500650h |pmid=24981631|pmc=4108183 }}</ref>

===Conjugation===
Glutathione facilitates [[Xenobiotic metabolism#Phase II – conjugation|metabolism of xenobiotics]]. [[Glutathione S-transferase|Glutathione ''S''-transferase]] enzymes catalyze its conjugation to [[lipophilic]] xenobiotics, facilitating their excretion or further metabolism.<ref>{{cite journal|title=Glutathione transferases |author=Hayes, John D. |author2=Flanagan, Jack U. |author3=Jowsey, Ian R. |journal=Annual Review of Pharmacology and Toxicology|year=2005|volume=45|pages=51–88|doi=10.1146/annurev.pharmtox.45.120403.095857|pmid=15822171}}</ref> The conjugation process is illustrated by the metabolism of [[NAPQI|''N''-acetyl-''p''-benzoquinone imine]] (NAPQI). NAPQI is a reactive [[metabolite]] formed by the action of [[cytochrome P450 oxidase|cytochrome P450]] on [[paracetamol]] (acetaminophen). Glutathione conjugates to NAPQI, and the resulting ensemble is excreted. As a result of this reaction cellular glutathione concentration tends to be depleted in presence of acetaminophen.

===In plants===
In plants, glutathione is involved in stress management. It is a component of the [[glutathione-ascorbate cycle]], a system that reduces poisonous [[hydrogen peroxide]].<ref name=Noctor >{{cite journal | vauthors = Noctor G, Foyer CH | title = Ascorbate and Glutathione: Keeping Active Oxygen Under Control | journal = Annual Review of Plant Physiology and Plant Molecular Biology | volume = 49 | issue = 1 | pages = 249–279 | date = June 1998 | pmid = 15012235 | doi = 10.1146/annurev.arplant.49.1.249 }}</ref> It is the precursor of [[phytochelatins]], glutathione [[oligomer]]s that [[chelate]] heavy metals such as [[cadmium]].<ref>{{cite journal | vauthors = Ha SB, Smith AP, Howden R, Dietrich WM, Bugg S, O'Connell MJ, Goldsbrough PB, Cobbett CS | title = Phytochelatin synthase genes from Arabidopsis and the yeast Schizosaccharomyces pombe | journal = The Plant Cell | volume = 11 | issue = 6 | pages = 1153–64 | date = June 1999 | pmid = 10368185 | pmc = 144235 | doi = 10.1105/tpc.11.6.1153 }}</ref> Glutathione is required for efficient defence against plant pathogens such as ''[[Pseudomonas syringae]]'' and ''[[Phytophthora]] brassicae''.<ref name=Parisy >{{cite journal | vauthors = Parisy V, Poinssot B, Owsianowski L, Buchala A, Glazebrook J, Mauch F | title = Identification of PAD2 as a gamma-glutamylcysteine synthetase highlights the importance of glutathione in disease resistance of Arabidopsis | journal = The Plant Journal | volume = 49 | issue = 1 | pages = 159–172 | date = January 2007 | pmid = 17144898 | doi = 10.1111/j.1365-313X.2006.02938.x | url = http://doc.rero.ch/record/6306/files/mauch_ipg.pdf | doi-access = free }}</ref> [[Adenylyl-sulfate reductase]], an enzyme of the [[sulfur assimilation]] pathway, uses glutathione as an electron donor. Other enzymes using glutathione as a substrate are [[glutaredoxin]]s. These small [[oxidoreductases]] are involved in flower development, [[salicylic acid]], and plant defence signalling.<ref name=Rouhier >{{cite journal | vauthors = Rouhier N, Lemaire SD, Jacquot JP | title = The role of glutathione in photosynthetic organisms: emerging functions for glutaredoxins and glutathionylation | journal = Annual Review of Plant Biology | volume = 59 | issue = 1 | pages = 143–166 | year = 2008 | pmid = 18444899 | doi = 10.1146/annurev.arplant.59.032607.092811 | bibcode = 2008AnRPB..59..143R | url = https://hal.inrae.fr/hal-02660326/file/2008%20Rouhier%20Jacquot%20ARPB.pdf }}</ref>