Glutathione (GSH)

Glutathione (GSH, L-gamma-Glutamyl-L-cysteinyl-glycine) is a tripeptide composed of glutamic acid, cysteine, and glycine, and is the most abundant intracellular low-molecular-weight antioxidant in biological systems. Its mechanism centres on its role as the master cellular redox buffer and electron donor in antioxidant enzyme systems. Glutathione exists in reduced (GSH) and oxidised (GSSG) forms; the GSH/GSSG ratio is a critical determinant of cellular redox status. GSH functions as a substrate for two major antioxidant enzyme systems: (1) Glutathione peroxidase (GPx) — GSH serves as the electron donor for GPx-catalysed reduction of hydrogen peroxide (H2O2) and lipid hydroperoxides to water and lipid alcohols, respectively, with GSH being oxidised to GSSG in the process. (2) Glutathione S-transferase (GST) — GSH conjugates with electrophilic substrates (xenobiotics, metabolic byproducts) via GST-catalysed reactions, forming water-soluble conjugates for cellular export and detoxification. Beyond enzymatic antioxidant activity, GSH directly scavenges reactive oxygen and nitrogen species through non-enzymatic reactions, regenerates other antioxidants (vitamins C and E) from their oxidised forms, and participates in protein S-glutathionylation — a post-translational modification that regulates protein function in redox signalling.