Glutathione and glutathione-related proteins (GSH system) (GSH system)

The glutathione (GSH) system is a fundamental cellular network comprising the tripeptide glutathione and a suite of enzymes and transporters dedicated to maintaining redox homeostasis and facilitating detoxification (Lushchak, 2012). The system's core includes the biosynthetic enzymes glutamate-cysteine ligase (GCL) and glutathione synthetase (GSS), as well as the cystine/glutamate transporter (System Xc-) which imports the essential precursor cysteine (Lu, 2013). Functional components include glutathione peroxidases (GPXs), which reduce hydrogen peroxide and lipid hydroperoxides, and glutathione S-transferases (GSTs), which conjugate GSH to electrophilic xenobiotics to promote their excretion (Traverso et al., 2013). In oncology, the GSH system is frequently hijacked by tumor cells to neutralize reactive oxygen species and evade ferroptosis, leading to chemotherapy and radiotherapy resistance (Dixon et al., 2012). Conversely, systemic GSH depletion is a hallmark of neurodegenerative disorders such as Parkinson's disease, where it exacerbates oxidative damage to neurons (StatPearls, 2023). Therapeutic interventions target this system through various modalities: N-acetylcysteine is used to replenish GSH levels in cases of oxidative stress or toxicity, while inhibitors like buthionine sulfoximine (BSO) and erastin are employed to deplete GSH and sensitize cancer cells to treatment (Kennedy et al., 2020).

Other names

Glutathione systemGSH-dependent enzymesThiol redox systemGlutathione metabolism pathway

GSH repletion, GCL inhibition, System Xc- inhibition, GST inhibition, GPX mimicry, GST-mediated prodrug activation, Nrf2 activation