Glutathione biosynthesis (Saccharomyces cerevisiae)

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1reduced glutathioneL-gamma-glutamylcysteineL-glycineATPphosphateADPphosphateGSH1GHS2L-cysteineATPL-glutamateADP


Description

The tripeptide glutathione (GSH: L-γ-glutamyl-L-cysteinylglycine) is a prevalent intracellular thiol that is able to act as a cellular redox buffer due to its low redox potential (as reviewed in (CITS: [12702279])). GSH is involved in many biological processes including: protein and DNA synthesis; amino acid transport; enzyme regulation; protection of cells against reactive oxygen compounds and free radicals, xenobiotics and heavy metals (as reviewed in (CITS: [12702279])). GSH can also be used as a source of sulfur and cysteine in (CITS: [1674526], [10514563]). GSH is synthesized from its constituent amino acids by two ATP-dependent steps (as reviewed in (CITS: [12702279])). In the first step γ-glutamylcysteine synthetase (Gsh1p) catalyzes the formation of the dipeptide γ-glutamylcysteine from glutamate and cysteine. In the second step, GSH synthetase (Gsh2p) catalyzes the ligation of glycine with γ-glutamylcysteine to form GSH. GSH is an essential reductant in yeast during normal metabolic processes (CITS: [8662189]), but the dipeptide γ-glutamylcysteine is able to substitute for GSH as an antioxidant (CITS: [9307967]). GSH biosynthesis is co-regulated by Met4p, a transcription factor that induces expression of genes involved in sulfur assimilation, by Yap1p, a stress-responsive transcription factor, and by GSH feedback inhibition, which inhibits both GSH1 expression and Gsh1p enzyme activity (CITS: [12406228], [14514673]). Expression of GSH1 and GSH2 is induced by oxidative stress in a Yap1p-dependent manner with subsequent increases in intracellular GSH content (CITS: [7915005], [10809786]). GSH1 is also transcriptionally up-regulated by the heavy metal cadmium in the presence of Met4p and the DNA-binding proteins Met31p and Met32p (CITS: [9044254], [10921921]). SOURCE: SGD pathways, http://pathway.yeastgenome.org/server.html

Comments

GenMAPP remarks 
Based on http://pathway.yeastgenome.org/biocyc/

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Bibliography

  1. Grant CM; ''Role of the glutathione/glutaredoxin and thioredoxin systems in yeast growth and response to stress conditions.''; Mol Microbiol, 2001 PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
117295view11:07, 20 May 2021EweitzModified title
76277view21:37, 25 June 2014Khanspersupdate
69819view14:36, 11 July 2013EgonwMarked a few DataNodes with CAS registry numbers as metabolites.
69600view20:31, 8 July 2013MaintBotUpdated to 2013 gpml schema
67295view10:33, 26 June 2013Christine ChichesterOntology Term : 'glutathione biosynthetic pathway' added !
41831view04:50, 2 March 2011MaintBotRemoved redundant pathway information and comments
36618view22:31, 9 April 2010MaintBotDescription and bibliography added from SGD
21091view11:30, 14 November 2008MaintBot[[Pathway:Saccharomyces cerevisiae:Glutathione Biosynthesis]] moved to [[Pathway:WP196]]: Moved to stable identifier
12726view08:00, 17 May 2008MaintBotautomated metabolite conversion
8750view14:08, 7 January 2008MaintBotAdded to category $category
8748view14:08, 7 January 2008M.BraymerUploaded new pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
ADP58-64-0 (CAS)
ATP1927-31-7 (CAS)
GHS2GeneProductS000005409 (SGD)
GSH1GeneProductS000003637 (SGD)
L-cysteine52-90-4 (CAS)
L-glutamate56-86-0 (CAS)
L-glycine56-40-6 (CAS)
phosphate14265-44-2 (CAS)

Annotated Interactions

No annotated interactions
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