Glutathione antioxidant pathway (GSH pathway)

The glutathione antioxidant pathway is a fundamental cellular defense system essential for maintaining redox homeostasis and protecting cells from oxidative damage (StatPearls, 2023). It revolves around the tripeptide glutathione (L-gamma-glutamyl-L-cysteinyl-glycine), which serves as a major endogenous antioxidant by neutralizing reactive oxygen species (ROS) and free radicals (PubChem, CID 124886). The pathway involves several key enzymes: Glutathione Peroxidase (GPX) reduces peroxides while oxidizing GSH to glutathione disulfide (GSSG), and Glutathione Reductase (GSR) restores GSH using NADPH as a reducing equivalent (UniProt, P00390). Additionally, Glutathione S-transferases (GSTs) facilitate the detoxification of xenobiotics by conjugating them with GSH for excretion (PubMed, PMID: 28254920). Dysregulation of this pathway is implicated in numerous diseases, including Parkinson's disease, where GSH depletion is a hallmark, and cancer, where overactive GSH synthesis can lead to multi-drug resistance (PubMed, PMID: 30031279). Therapeutic strategies include the use of N-acetylcysteine to boost GSH levels in respiratory or toxicological conditions, or Buthionine sulfoximine to deplete GSH in tumor cells to enhance the efficacy of chemotherapy and induce ferroptosis (NIH, 2022).

Other names

Glutathione systemGSH redox systemGlutathione metabolismGSH-GSSG cycleGlutathione-mediated detoxification

Modulation of glutathione levels or activity of associated enzymes (e.g., GPX, GSR, GST) to restore redox balance or induce oxidative stress-mediated cell death in malignant cells.