Cellular glutathione redox system (GSH system)

The cellular glutathione redox system is a fundamental biochemical network responsible for maintaining intracellular redox homeostasis and protecting cells from oxidative damage. It primarily consists of the tripeptide glutathione (GSH), its oxidized disulfide form (GSSG), and a suite of enzymes including glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione S-transferase (GST) [1][2]. GSH acts as a potent antioxidant by directly scavenging reactive oxygen species (ROS) or serving as a cofactor for GPx to neutralize hydrogen peroxide and lipid hydroperoxides [3]. Beyond antioxidant defense, the system plays a critical role in the detoxification of xenobiotics and the regulation of various cellular processes, including apoptosis and signal transduction [4]. In clinical contexts, the glutathione system is a double-edged sword; while its depletion is associated with neurodegenerative disorders and acute liver failure (notably in acetaminophen toxicity), its upregulation in many cancer types contributes to multi-drug resistance and tumor survival [5][6]. Pharmacological modulation of this system includes the use of N-acetylcysteine to replenish GSH stores and buthionine sulfoximine to deplete GSH in order to sensitize cancer cells to therapy [7]. Recent research also focuses on the system's role in ferroptosis, where inhibition of glutathione-dependent enzymes like GPX4 leads to iron-dependent lipid peroxidation and cell death [8].

Other names

Glutathione systemGSH/GSSG redox coupleGlutathione antioxidant systemGlutathione metabolic pathway

Glutathione replenishment, Glutathione depletion, Inhibition of glutathione synthesis, Glutathione peroxidase mimicry, Induction of ferroptosis, Inhibition of cystine/glutamate antiporter