Glutathione metabolic pathway

The glutathione metabolic pathway encompasses the synthesis, recycling, and utilization of glutathione (GSH), a tripeptide (γ-glutamyl-cysteinyl-glycine) pivotal for maintaining cellular redox homeostasis and detoxification capacity[7][4][1]. Glutathione is synthesized in a two-step process involving γ-glutamylcysteine synthetase and glutathione synthetase[4]. The pathway includes several key enzymes such as glutathione S-transferases (GSTs), which conjugate GSH to xenobiotics for detoxification[6][1]; glutathione peroxidases, which use GSH to neutralize peroxides[7][1]; glutathione reductase, which restores reduced GSH from the oxidized form (GSSG)[7]; and γ-glutamyl transferase (GGT), which modulates extracellular GSH recycling[5][9]. Dysregulation of the glutathione pathway is linked to increased drug resistance in cancer (due mainly to GSTs and GGT)[6][3][5][8][2], a variety of chronic diseases, and heightened susceptibility to oxidative injury[10][7][1]. Though the pathway itself is not a drug target, its component enzymes and metabolic fluxes are actively exploited or modulated by several classes of anticancer and cytoprotective drugs[3][1][5][9][6][8].

Other names

Glutathione biosynthesis pathwayγ-glutamyl cycleGSH metabolic pathway

Scavenging of reactive oxygen species via glutathione peroxidase activity Detoxification of xenobiotics by conjugation (mainly via GST) Regeneration of reduced glutathione from oxidized form, catalyzed by glutathione reductase Cysteine/GSH pool maintenance via γ-glutamyl cycle enzymes