Subsystem: Glutathione: Biosynthesis and gamma-glutamyl cycle

This subsystem's description is:

Glutathione (GSH) is a tripeptide (gamma-Glu-Cys-Gly), which is present in high concentration in most living cells from microorganisms to man. The biological importance of GSH is mainly related to the free sulphydryl moiety of Cys residue, which confers unique redox (Eo=-0.24) and nucleophilic properties. GSH servers a pivotal role in numerous and very diverse cellular functions, including free radical scavenging, redox reactions, formation of deoxyribonucleotides, detoxication of xenobiotics, amino acid transport and leukotriene biosynthesis (in eukaryotes), and many others. Main forms of GHS include:
(i) reduced GSH,
(ii) oxidized GSSG and
(iii) mixed disulfides: mostly GSS-protein and GSSR (R = suitable residue such as cysteine or CoASH). For example, CoASSG is a major component of the CoA pool in yeast and E. coli (Loewen 1981)
(iv) thiol esters, which function as intermediates in metabolism of certain compounds, such as methylglyoxal and formaldehyde
(v) another interesting derivative is the covalent addict GSH-spermidine formed at the end of exponential growth in E. coli (Tabor and Tabor, 1979) and in trypanosomatids (encoded in Subsystem: Glutathionylspermidine and Trypanothione)

Under unstressed physiological conditions much of the thipeptide is present in the free reduced form. In E. coli GSH content is very high and accounts for more than 1% of dry cell weight. The concentration of oxidized form is usually much smaller, with the GSH/GSSG ratio generally being greater than 50. This balance is maintained by GSH reductase (at the expense of NADPH), ensuring a cellular environment where essential sulphygryl groups of key enzymes and co-enzymes are protected.

In higher eukaryotes glutathione metabolism proceeds through gamma-glutamyl cycle. Complete core cycle involves six enzymes (see Tab "Illustrations"): gamma-glutamyl cysteine synthetase, GSH synthetase, gamma-glutamyl transpeptidase, gamma-glutamyl cyclotransferase, 5-oxoprolinase, and dipeptidase (and additional peptidases in some organisms) (Meister, 1985). However, gamma-glutamyl cycle in microbes apparently differs from that in mammals in that activities of gamma-glutamyl cyclotransferase and 5-oxoprolinase are excluded and bypassed by gamma-glutamyl transpeptidase. This truncated version of the cycle involves:
(i) the biosynthetic enzymes (encoded also in SS: Glutathione Biosynthesis”)
(ii) Gamma-glutamyltranspeptidase,
(iii) Cystein-glycine dipeptidase (or other peptidases)

Gamma-glutamyl-cyclotransferase and 5-oxoprolinase are probably NOT present in lower euks (yeast) and microbes, but the issue is still being debated (for example, see review by (Penninckx and Elkens, 1993)

For more information, please check out the description and the additional notes tabs, below

DiagramFunctional RolesSubsystem SpreadsheetDescriptionAdditional NotesScenarios 
Group Alias
Abbrev.Functional RoleReactionsScenario ReactionsGOLiterature

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