Glutathione

Source: Wikipedia, the free encyclopedia.

Glutathione[1]
Names
IUPAC name
γ-Glutamylcysteinylglycine
Systematic IUPAC name
(2S)-2-Amino-5-({(2R)-1-[(carboxymethyl)amino]-1-oxo-3-sulfanylpropan-2-yl}amino)-5-oxopentanoic acid
Other names
γ-L-Glutamyl-L-cysteinylglycine
(2S)-2-Amino-4-({(1R)-1-[(carboxymethyl)carbamoyl]-2-sulfanylethyl}carbamoyl)butanoic acid
Identifiers
3D model (
JSmol
)
Abbreviations GSH
ChEBI
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard
 100.000.660 Edit this at Wikidata
IUPHAR/BPS
KEGG
MeSH Glutathione
UNII
  • InChI=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 checkY
    Key: RWSXRVCMGQZWBV-WDSKDSINSA-N checkY
  • C(CC(=O)N[C@@H](CS)C(=O)NCC(=O)O)[C@@H](C(=O)O)N
Properties
C10H17N3O6S
Molar mass 307.32 g·mol−1
Melting point 195 °C (383 °F; 468 K)[1]
Freely soluble[1]
Solubility in methanol, diethyl ether Insoluble[1]
Pharmacology
V03AB32 (WHO)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
checkY verify (what is checkY☒N ?)

Glutathione (GSH,

glutamate side chain and cysteine. The carboxyl group of the cysteine residue is attached by normal peptide linkage to glycine
.

Biosynthesis and occurrence

Glutathione biosynthesis involves two adenosine triphosphate-dependent steps:

While all animal cells are capable of synthesizing glutathione, glutathione synthesis in the liver has been shown to be essential. GCLC knockout mice die within a month of birth due to the absence of hepatic GSH synthesis.[4][5]

The unusual gamma amide linkage in glutathione protects it from hydrolysis by peptidases.[6]

Occurrence

Glutathione is the most abundant non-protein

mitochondria.[8]

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.[9][10]

Systemic availability of orally consumed glutathione has poor bioavailability because the tripeptide is the substrate of

alimentary canal, and due to the absence of a specific carrier of glutathione at the level of cell membrane.[11][12] The administration of N-acetylcysteine (NAC), a cysteine prodrug, helps replenish intracellular GSH levels.[13] The patented compound RiboCeine has been studied as a supplement that enhances production of glutathione which helps mitigate hyperglycemia.[14][15]

Biochemical function

Glutathione exists in reduced (GSH) and oxidized (GSSG) states.[16] The ratio of reduced glutathione to oxidized glutathione within cells is a measure of cellular oxidative stress[17][8] 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

NADPH.[18] 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.[19][6] This conversion is illustrated by the reduction of peroxides:

2 GSH + R2O2 → GSSG + 2 ROH  (R = H, alkyl)

and with free radicals:

GSH + R• → 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:[20]

RSH + GSH + [O] → GSSR + H2O

Glutathione is also employed for the detoxification of

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.[21][22][23]

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 the storage of cysteine. Glutathione enhances the function of citrulline as part of the nitric oxide cycle.[24] It is a cofactor and acts on glutathione peroxidase.[25] Glutathione is used to produce S-sulfanylglutathione, which is part of hydrogen sulfide metabolism.[26]

Conjugation

Glutathione facilitates

cytochrome P450 on paracetamol
(acetaminophen). Glutathione conjugates to NAPQI, and the resulting ensemble is excreted.

In plants

In plants, glutathione is involved in stress management. It is a component of the

oxidoreductases are involved in flower development, salicylic acid, and plant defence signalling.[31]

Uses

Winemaking

The content of glutathione in

caffeoyltartaric acid quinones generated by enzymic oxidation as grape reaction product.[32] Its concentration in wine can be determined by UPLC-MRM mass spectrometry.[33]

See also

References

  1. ^
    ISBN 9781498754293
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  6. ^
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  7. PMID 6020678
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  8. ^
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  10. ISBN 978-1-4020-0178-9
    – via Google Books.
  11. S2CID 27606314
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  12. ^ "Acetylcysteine Monograph for Professionals". Drugs.com.
  13. PMID 17602868
    .
  14. ^ Nagasawa, Herbert T. (27 November 2014). "COMPOSITIONS COMPRISING SUGAR-CYSTEINE PRODUCTS - US-20140348811-A1". ppubs.uspto.gov. United States Patent Office. p. 16. Retrieved 31 October 2023. 30. A method of increasing ATP and/or glutathione...
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  18. PMID 23631642
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  20. PMID 19135374
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  21. S2CID 452394
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  22. S2CID 85414084
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  23. S2CID 4273230
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  24. PMID 10368185
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  25. S2CID 6467802
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  27. PMID 15822171
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  32. doi:10.1002/jsfa.2740570107
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  33. PMID 25457918
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