Glutathione redox system (GSH system) (GSH system)

The glutathione redox system is a fundamental cellular defense mechanism composed of the tripeptide glutathione (GSH) and a suite of enzymes, including glutathione peroxidase (GPx) and glutathione reductase (GR) (StatPearls, 2023). Its primary biological function is to maintain intracellular redox homeostasis by scavenging reactive oxygen species (ROS) and detoxifying electrophilic compounds (PubMed, PMID: 24513455). In the context of disease, cancer cells often exploit this system to survive high levels of oxidative stress and develop resistance to platinum-based chemotherapies (Nature Reviews Cancer, 2019). Conversely, glutathione depletion is a hallmark of neurodegenerative conditions like Parkinson's disease, where accumulated oxidative damage contributes to neuronal loss (PubMed, PMID: 22503478). Pharmacological intervention targets this system through various means: N-acetylcysteine (NAC) acts as a precursor to boost GSH levels, while agents like buthionine sulfoximine (BSO) or erastin deplete GSH to induce ferroptosis in tumor cells (Cell, 2012). Monitoring the GSH/GSSG ratio and lipid peroxidation markers serves as a key method for assessing the efficacy of these redox-modulating therapies (UniProt, 2024).

Other names

Glutathione-dependent antioxidant systemGSH/GSSG redox coupleCellular redox homeostasis systemGlutathione metabolic pathway

Inhibition of glutathione biosynthesis, enzymatic inhibition of glutathione peroxidase 4 (GPX4), replenishment of intracellular glutathione precursors, and direct neutralization of reactive oxygen species.