Glutathione

Glutathione (GSH) is a tripeptide, γ-L-glutamyl-L-cysteinyl-glycine (C10H17N3O6S, 307.32 g/mol), in which glutamate is joined to cysteine through a γ-glutamyl linkage and the cysteine supplies a free thiol group. It is the most abundant low-molecular-mass thiol in animal cells, and the reduced glutathione/glutathione disulfide (GSH/GSSG) pair is the major cellular redox couple. GSH is synthesized from glutamate, cysteine and glycine by two sequential cytosolic enzymes, γ-glutamylcysteine synthetase and GSH synthetase.

Glutathione in the research literature

Biochemical work on glutathione has examined how its synthesis is controlled, and reviews identify γ-glutamylcysteine synthetase activity, cysteine availability and feedback inhibition by GSH as the principal regulatory points. Nutritional studies in animal models link protein supply to the maintenance of tissue GSH homeostasis. Glutathione has been studied for roles in antioxidant defense, nutrient metabolism, gene expression, signal transduction, cytokine production and protein glutathionylation.

Related enzymology has focused on the glutathione peroxidase (GPx) family, which reduces hydroperoxides. The cytosolic enzyme GPx1 was established as the first selenoenzyme described in vertebrates, and mechanistic studies using density functional theory and NMR of model compounds describe a selenolate being oxidized to a selenenic acid during the catalytic reaction.