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===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 the [[organelle]]s.<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 ΞΌM), 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=2β12 |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 = 149β152 | 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 [[eukaryote]]s do not, including some members of [[Fabaceae]], ''[[Entamoeba]]'', and ''[[Giardia]]''. The only known [[archaea]] that make glutathione are [[Haloarchaea|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 | pages = 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> Systemic availability of orally consumed glutathione is poor. It had 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 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 = 667β9 | 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 β 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=355β9 |doi=10.1016/j.coph.2007.04.005 |pmid=17602868 }}</ref>
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