Glutathione

{{Short description|Ubiquitous antioxidant compound in living organisms}} {{Use dmy dates|date=August 2021}} {{Chembox | Watchedfields = changed | verifiedrevid = 443838068 | Reference = <ref name=crc/> | ImageFile = Glutathione-skeletal.svg | ImageClass = skin-invert-image | ImageFile2 = Glutathione-from-xtal-3D-balls.png | ImageClass2 = bg-transparent | ImageFile3 = Glutathione-3D-vdW.png | ImageClass3 = bg-transparent | IUPACName = γ-Glutamylcysteinylglycine | SystematicName = (2''S'')-2-Amino-5-({(2''R'')-1-[(carboxymethyl)amino]-1-oxo-3-sulfanylpropan-2-yl}amino)-5-oxopentanoic acid | OtherNames = γ-L-Glutamyl-L-cysteinylglycine (2''S'')-2-Amino-4-({(1''R'')-1-[(carboxymethyl)carbamoyl]-2-sulfanylethyl}carbamoyl)butanoic acid |Section1={{Chembox Identifiers | IUPHAR_ligand = 6737 | Abbreviations = GSH | UNII_Ref = {{fdacite|correct|FDA}} | UNII = GAN16C9B8O | ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL = 1543 | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 1S/C10H17N3O6S/c11-5(10(18)19)1-2-7(14)13-6(4-20)9(17)12-3-8(15)16/h5-6,20H,1-4,11H2,(H,12,17)(H,13,14)(H,15,16)(H,18,19)/t5-,6-/m0/s1 | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = RWSXRVCMGQZWBV-WDSKDSINSA-N | CASNo = 70-18-8 | CASNo_Ref = {{cascite|correct|CAS}} | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 111188 | PubChem = 124886 | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank = DB00143 | ChEBI_Ref = {{ebicite|correct|EBI}} | ChEBI = 16856 | KEGG_Ref = {{keggcite|correct|kegg}} | KEGG = C00051 | SMILES = C(CC(=O)N[C@@H](CS)C(=O)NCC(=O)O)[C@@H](C(=O)O)N | MeSHName = Glutathione }} |Section2={{Chembox Properties | C=10 | H=17 | N=3 | O=6 | S=1 | Appearance = | Density = | MeltingPtC = 195 | MeltingPt_ref = <ref name=crc>{{cite book | editor-last= Haynes |editor-first=William M. | name-list-style = vanc| date = 2016| title = CRC Handbook of Chemistry and Physics | edition = 97th | publisher = CRC Press | isbn = 978-1-4987-5429-3|page=3.284| title-link = CRC Handbook of Chemistry and Physics}}</ref> | BoilingPt = | Solubility = Freely soluble<ref name=crc/> | SolubleOther = Insoluble<ref name=crc/> | Solvent = methanol, diethyl ether }} |Section6={{Chembox Pharmacology | ATCCode_prefix = V03 | ATCCode_suffix = AB32 }} |Section7={{Chembox Hazards | MainHazards = | FlashPt = | AutoignitionPt = }} }} thumb|Glutathione (GSH) powder

'''Glutathione''' ('''GSH''', {{IPAc-en|ˌ|ɡ|l|uː|t|ə|ˈ|θ|aɪ|əʊ|n}}) is a tripeptide made of the amino acids glutamate, cysteine, and glycine. It is an antioxidant in plants, animals, fungi, and some bacteria and archaea. Glutathione is capable of preventing damage to important cellular components caused by sources such as reactive oxygen species, free radicals, peroxides, lipid peroxides, and heavy metals.<ref>{{cite journal | vauthors=Pompella A, Visvikis A, Paolicchi A, De Tata V, Casini AF | title=The changing faces of glutathione, a cellular protagonist | journal=Biochemical Pharmacology | volume=66 | issue=8 | pages=1499–1503 | date=October 2003 | pmid=14555227 | doi=10.1016/S0006-2952(03)00504-5 }}</ref>

It is synthesized by attaching cysteine to the carboxyl group of the glutamate side chain with a gamma peptide linkage, and to glycine with a normal peptide bond.

==Biosynthesis and occurrence== Glutathione biosynthesis involves two adenosine triphosphate-dependent steps: *First, γ-glutamylcysteine is synthesized from L-glutamate and L-cysteine. This conversion requires the enzyme glutamate–cysteine ligase (GCL, glutamate-cysteine synthase). This reaction is the rate-limiting step in glutathione synthesis.<ref>{{cite journal | vauthors=White CC, Viernes H, Krejsa CM, Botta D, Kavanagh TJ | title=Fluorescence-based microtiter plate assay for glutamate-cysteine ligase activity | journal=Analytical Biochemistry | volume=318 | issue=2 | pages=175–180 | date=July 2003 | pmid=12814619 | doi=10.1016/S0003-2697(03)00143-X | url=https://zenodo.org/record/1259521 }}</ref> *Second, glycine is added to the C-terminal of γ-glutamylcysteine. This condensation is catalyzed by glutathione synthetase.

While all animal cells are capable of synthesizing glutathione, synthesis in the liver is essential. GCLC knockout mice die within a month of birth due to the absence of hepatic GSH synthesis.<ref>{{cite journal | vauthors=Chen Y, Yang Y, Miller ML, Shen D, Shertzer HG, Stringer KF, Wang B, Schneider SN, Nebert DW, Dalton TP | title=Hepatocyte-specific Gclc deletion leads to rapid onset of steatosis with mitochondrial injury and liver failure | journal=Hepatology | volume=45 | issue=5 | pages=1118–28 | date=May 2007 | pmid=17464988 | doi=10.1002/hep.21635 | s2cid=25000753 | doi-access=free }}</ref><ref name="Sies 916–921">{{cite journal | vauthors=Sies H | title=Glutathione and its role in cellular functions | journal=Free Radical Biology & Medicine | volume=27 | issue=9–10 | pages=916–921 | year=1999 | pmid=10569624 | doi=10.1016/S0891-5849(99)00177-X }}</ref>

The unusual gamma amide linkage in glutathione protects it from hydrolysis by peptidases.<ref name=Wu/>

===Occurrence=== Glutathione is the most abundant non-protein thiol ({{chem2|R\sSH}}-containing compound) in animal cells, ranging from 0.5 to 10 mmol/L. It is present in the cytosol and organelles.<ref name="Wu" /> The concentration of glutathione in the cytoplasm is significantly higher (ranging from 0.5-10 mM) compared to extracellular fluids (2-20 μM), reaching levels up to 1000 times greater.<ref>{{cite journal |vauthors=Giustarini D, Milzani A, Dalle-Donne I, Rossi R |title=How to Increase Cellular Glutathione |journal=Antioxidants |volume=12 |issue=5 |date=May 2023 |page=1094 |pmid=37237960 |pmc=10215789 |doi=10.3390/antiox12051094 |doi-access=free }}</ref><ref>{{cite journal |vauthors=Cheng R, Feng F, Meng F, Deng C, Feijen J, Zhong Z |title=Glutathione-responsive nano-vehicles as a promising platform for targeted intracellular drug and gene delivery |journal=J Control Release |volume=152 |issue=1 |pages=2–12 |date=May 2011 |pmid=21295087 |doi=10.1016/j.jconrel.2011.01.030 }} </ref> In healthy cells and tissue, more than 90% of the total glutathione pool is in the reduced form (GSH), with the remainder in the disulfide form (GSSG).<ref name="pmid6020678">{{cite journal | vauthors=Halprin KM, Ohkawara A | title=The measurement of glutathione in human epidermis using glutathione reductase | journal=The Journal of Investigative Dermatology | volume=48 | issue=2 | pages=149–152 | year=1967 | pmid=6020678 | doi=10.1038/jid.1967.24 | doi-access=free }}</ref> The cytosol holds 80-85% of cellular GSH, and the mitochondria hold 10-15%.<ref name="pmid22995213" />

Human beings synthesize glutathione, but a few eukaryotes do not, including some members of Fabaceae, ''Entamoeba'', and ''Giardia''. The only known archaea that make glutathione are halobacteria. Some bacteria, such as "Cyanobacteria" and Pseudomonadota, can biosynthesize glutathione.<ref>{{cite journal | vauthors=Copley SD, Dhillon JK | title=Lateral gene transfer and parallel evolution in the history of glutathione biosynthesis genes | journal=Genome Biology | volume=3 | issue=5 | article-number=research0025 | date=29 April 2002 | pmid=12049666 | pmc=115227 | doi=10.1186/gb-2002-3-5-research0025 | doi-access=free }}</ref><ref>{{Cite book|url=https://books.google.com/books?id=aX2eJf1i67IC|title=Significance of glutathione in plant adaptation to the environment|last1=Wonisch|first1=Willibald|last2=Schaur|first2=Rudolf J. | name-list-style=vanc | publisher=Springer|year=2001|isbn=978-1-4020-0178-9|editor-last=Grill|editor-first=D.|chapter=Chapter 2: Chemistry of Glutathione|editor-last2=Tausz|editor-first2=T.|editor-last3=De Kok|editor-first3=L.J.|chapter-url=https://books.google.com/books?id=aX2eJf1i67IC&pg=PA13|via=Google Books}}</ref>

The systemic availability of orally administered glutathione is poor. It has low bioavailability because the tripeptide is the substrate of proteases (peptidases) of the alimentary canal, and due to the absence of a specific ''carrier'' of glutathione at the level of the cell membrane.<ref>{{cite journal | vauthors=Witschi A, Reddy S, Stofer B, Lauterburg BH | title=The systemic availability of oral glutathione | journal=European Journal of Clinical Pharmacology | volume=43 | issue=6 | pages=667–9 | year=1992 | pmid=1362956 | doi=10.1007/bf02284971 | s2cid=27606314 }}</ref><ref>{{Cite web|url=https://www.drugs.com/monograph/acetylcysteine.html|title=Acetylcysteine Monograph for Professionals|website=Drugs.com}}</ref> The administration of N-acetylcysteine (NAC), a cysteine prodrug, helps replenish intracellular GSH levels.<ref>{{Cite journal|title=N-acetylcysteine — a safe antidote for cysteine/glutathione deficiency|date=2007 |pmc=4540061 |last1=Atkuri |first1=K. R. |last2=Mantovani |first2=J. J. |last3=Herzenberg |first3=L. A. |last4=Herzenberg |first4=L. A. |journal=Current Opinion in Pharmacology |volume=7 |issue=4 |pages=355–9 |doi=10.1016/j.coph.2007.04.005 |pmid=17602868 }}</ref>

==Biochemical function== Glutathione exists in reduced (GSH) and oxidized (GSSG) states.<ref name="Iskusnykh">{{cite journal |vauthors=Iskusnykh IY, Zakharova AA, Pathak D |title=Glutathione in Brain Disorders and Aging |journal=Molecules |volume=27 |issue=1 |date=January 2022 |page=324 |pmid=35011559 |pmc=8746815 |doi=10.3390/molecules27010324 |url= |doi-access=free }}</ref> The ratio of reduced glutathione to oxidized glutathione within cells is a measure of cellular oxidative stress<ref>{{cite journal | vauthors=Pastore A, Piemonte F, Locatelli M, Lo Russo A, Gaeta LM, Tozzi G, Federici G | title=Determination of blood total, reduced, and oxidized glutathione in pediatric subjects | journal=Clinical Chemistry | volume=47 | issue=8 | pages=1467–9 | date=August 2001 | pmid=11468240 | doi= 10.1093/clinchem/47.8.1467| url=http://www.clinchem.org/content/47/8/1467.long | doi-access=free }}</ref><ref name="pmid22995213">{{cite journal | author=Lu SC | title=Glutathione synthesis | journal= Biochimica et Biophysica Acta (BBA) - General Subjects| volume=1830 | issue=5 | pages=3143–53 | date=May 2013 | pmid=22995213 | pmc=3549305 | doi=10.1016/j.bbagen.2012.09.008 }}</ref> where increased GSSG-to-GSH ratio is indicative of greater oxidative stress.

In the reduced state, the thiol group of cysteinyl residue is a source of one reducing equivalent. Glutathione disulfide (GSSG) is thereby generated. The oxidized state is converted to the reduced state by NADPH.<ref name="Couto2013">{{cite journal | vauthors=Couto N, Malys N, Gaskell SJ, Barber J | title=Partition and turnover of glutathione reductase from Saccharomyces cerevisiae: a proteomic approach | journal=Journal of Proteome Research | volume=12 | issue=6 | pages=2885–94 | date=June 2013 | pmid=23631642 | doi=10.1021/pr4001948 | url=https://pure.manchester.ac.uk/ws/files/27512240/POST-PEER-REVIEW-PUBLISHERS.PDF }}</ref> This conversion is catalyzed by glutathione reductase:

: NADPH + GSSG + H2O → 2 GSH + NADP+ + OH−

==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 + R2O2 → GSSG + 2 ROH {{pad|2em}}(R = H, alkyl) and with free radicals: : GSH + R• → {{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 + H2O

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''-D-lactoylglutathione. Glyoxalase II (EC 3.1.2.6) catalyzes the hydrolysis of ''S''-D-lactoylglutathione to glutathione and D-lactic acid.

It maintains exogenous antioxidants such as vitamins C and 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 leukotrienes and prostaglandins. It plays a role in cysteine storage. 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 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 metabolism of xenobiotics. 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 ''N''-acetyl-''p''-benzoquinone imine (NAPQI). NAPQI is a reactive metabolite formed by the action of 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 the presence of acetaminophen.

===In plants=== In plants, glutathione plays a role in stress response. 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 oligomers 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 defense 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 glutaredoxins. These small oxidoreductases are involved in flower development, salicylic acid, and plant defense 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>

==In degradation of drug delivery systems== Among various types of cancer, lung cancer, larynx cancer, mouth cancer, and breast cancer exhibit higher concentrations (10-40 mM) of GSH compared to healthy cells.<ref>{{cite journal |vauthors=Gamcsik MP, Kasibhatla MS, Teeter SD, Colvin OM |title=Glutathione levels in human tumors |journal=Biomarkers |volume=17 |issue=8 |pages=671–91 |date=December 2012 |pmid=22900535 |pmc=3608468 |doi=10.3109/1354750X.2012.715672 }}</ref> Thus, drug delivery systems containing disulfide bonds, typically cross-linked micro-nanogels, stand out for their ability to degrade in the presence of high concentrations of glutathione (GSH).<ref>{{cite journal |vauthors=Patra JK, Das G, Fraceto LF, Campos EV, Rodriguez-Torres MD, Acosta-Torres LS, Diaz-Torres LA, Grillo R, Swamy MK, Sharma S, Habtemariam S, Shin HS |title=Nano based drug delivery systems: recent developments and future prospects |journal=J Nanobiotechnology |volume=16 |issue=1 |article-number=71 |date=September 2018 |pmid=30231877 |pmc=6145203 |doi=10.1186/s12951-018-0392-8 |doi-access=free}}</ref> This degradation process releases the drug payload specifically into cancerous or tumorous tissue, leveraging the significant difference in redox potential between the oxidizing extracellular environment and the reducing intracellular cytosol.<ref>{{cite journal |vauthors=Li Y, Maciel D, Rodrigues J, Shi X, Tomás H |title=Biodegradable Polymer Nanogels for Drug/Nucleic Acid Delivery |journal=Chem Rev |volume=115 |issue=16 |pages=8564–8608 |date=August 2015 |pmid=26259712 |doi=10.1021/cr500131f }}</ref><ref>{{cite journal |vauthors=Adamo G, Grimaldi N, Campora S, Sabatino MA, Dispenza C, Ghersi G |title=Glutathione-Sensitive Nanogels for Drug Release |journal=Chemical Engineering Transactions |volume=38 |pages=457–462 |date=2014 |doi= |url=https://www.cetjournal.it/index.php/cet/article/view/5682}}</ref>

When internalized by endocytosis, nanogels encounter high concentrations of GSH inside the cancer cell. GSH, a potent reducing agent, donates electrons to disulfide bonds in the nanogels, initiating a thiol-disulfide exchange reaction. This reaction breaks the disulfide bonds, converting them into two thiol groups, and facilitates targeted drug release where it is needed most. This reaction is called a thiol-disulfide exchange reaction.<ref>{{cite book |first=H.F. |last=Gilbert |chapter=Molecular and Cellular Aspects of Thiol–Disulfide Exchange |title=Advances in Enzymology and Related Areas of Molecular Biology |publisher= |volume=63 |date=1990 |isbn=978-0-470-12309-6 |pages=69–172 |doi=10.1002/9780470123096.ch2 |pmid=2407068}}</ref><ref>{{cite book |first=H.F. |last=Gilbert |chapter=Thiol/disulfide exchange equilibria and disulfide bond stability |title=Biothiols, Part A: Monothiols and Dithiols, Protein Thiols, and Thiyl Radicals |series=Methods in Enzymology |publisher= |volume=251 |date=1995 |isbn=978-0-12-182152-4 |pages=8–28 |doi=10.1016/0076-6879(95)51107-5 |pmid=7651233}}</ref>

: R−S−S−R' + 2 GSH → R−SH + R'−SH + GSSG

where R and R' are parts of the micro-nanogel structure, and GSSG is oxidized glutathione (glutathione disulfide).

The breaking of disulfide bonds causes the nanogel to degrade into smaller fragments. This degradation process leads to the release of encapsulated drugs. The released drug molecules can then exert their therapeutic effects, such as inducing apoptosis in cancer cells.<ref>{{cite journal |vauthors=Elkassih SA, Kos P, Xiong H, Siegwart DJ |title=Degradable redox-responsive disulfide-based nanogel drug carriers via dithiol oxidation polymerization |journal=Biomater Sci |volume=7 |issue=2 |pages=607–617 |date=January 2019 |pmid=30462102 |pmc=7031860 |doi=10.1039/c8bm01120f }}</ref>

== Uses == ===Winemaking=== The content of glutathione in must, the first raw form of wine, determines the browning, or caramelizing effect, during the production of white wine by trapping the caffeoyltartaric acid quinones generated by enzymic oxidation as grape reaction product.<ref>{{cite journal | vauthors=Rigaud J, Cheynier V, Souquet JM, Moutounet M | name-list-style=vanc | year=1991 | title=Influence of must composition on phenolic oxidation kinetics | journal=Journal of the Science of Food and Agriculture | volume=57 | issue=1| pages=55–63 | doi=10.1002/jsfa.2740570107 | title-link=must | bibcode=1991JSFA...57...55R }}</ref> Its concentration in wine can be determined by UPLC-MRM mass spectrometry.<ref>{{cite journal | vauthors=Vallverdú-Queralt A, Verbaere A, Meudec E, Cheynier V, Sommerer N | title=Straightforward method to quantify GSH, GSSG, GRP, and hydroxycinnamic acids in wines by UPLC-MRM-MS | journal=Journal of Agricultural and Food Chemistry | volume=63 | issue=1 | pages=142–9 | date=January 2015 | pmid=25457918 | doi=10.1021/jf504383g | bibcode=2015JAFC...63..142V }}</ref>

== See also == * Reductive stress * Glutathione synthetase deficiency * Ophthalmic acid * roGFP, a tool to measure the cellular glutathione redox potential * Glutathione-ascorbate cycle * Bacterial glutathione transferase * Thioredoxin, a cysteine-containing small protein with very similar functions to reducing agents * Glutaredoxin, an antioxidant protein that uses reduced glutathione as a cofactor and is reduced nonenzymatically by it * Bacillithiol * Mycothiol * γ-L-Glutamyl-L-cysteine

== References == {{Reflist}}

{{Antioxidants}} {{Antidotes}} {{Enzyme cofactors}} {{Amino acid metabolism intermediates}} {{Glutamatergics}} {{Authority control}}

Category:Thiols Category:Tripeptides Category:Antioxidants Category:Skin whitening