Glutathione biosynthesis (WP196)
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: )). 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: )). GSH can also be used as a source of sulfur and cysteine in (CITS: , ). GSH is synthesized from its constituent amino acids by two ATP-dependent steps (as reviewed in (CITS: )). 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: ), but the dipeptide γ-glutamylcysteine is able to substitute for GSH as an antioxidant (CITS: ). 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: , ). Expression of GSH1 and GSH2 is induced by oxidative stress in a Yap1p-dependent manner with subsequent increases in intracellular GSH content (CITS: , ). 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: , ). SOURCE: SGD pathways, http://pathway.yeastgenome.org/server.html
AuthorsMeredith Braymer , Christine Chichester , Egon Willighagen , Kristina Hanspers , and Eric Weitz
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Pathway Ontologyglutathione biosynthetic pathway