Glutathione biosynthesis (WP196)

Saccharomyces cerevisiae

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,


Meredith Braymer , Christine Chichester , Egon Willighagen , Kristina Hanspers , and Eric Weitz


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Saccharomyces cerevisiae



Pathway Ontology

glutathione biosynthetic pathway


Label Type Compact URI Comment
L-glutamate Metabolite cas:56-86-0
L-cysteine Metabolite cas:52-90-4
ATP Metabolite cas:1927-31-7
ADP Metabolite cas:58-64-0
phosphate Metabolite cas:14265-44-2
ATP Metabolite cas:1927-31-7
L-glycine Metabolite cas:56-40-6
phosphate Metabolite cas:14265-44-2
ADP Metabolite cas:58-64-0
L-gamma-glutamyl-L-cysteine Metabolite chemspider:110467
GSH1 GeneProduct sgd:S000003637
GHS2 GeneProduct sgd:S000005409


  1. Role of the glutathione/glutaredoxin and thioredoxin systems in yeast growth and response to stress conditions. Grant CM. Mol Microbiol. 2001 Feb;39(3):533–41. PubMed Europe PMC Scholia