Glutathione synthesis and redox pathway enzymes (GSH pathway enzymes)

The glutathione synthesis and redox pathway enzymes represent a coordinated enzymatic network essential for maintaining cellular redox balance and protecting against oxidative and electrophilic stress (Creative Proteomics, 2024). This pathway includes the de novo synthesis enzymes glutamate-cysteine ligase (GCL) and glutathione synthetase (GSS), as well as the redox cycling enzymes glutathione peroxidase (GPX) and glutathione reductase (GSR) (NIH, 2023). Glutathione (GSH), the primary product, serves as a major antioxidant and a substrate for glutathione S-transferases (GST) in the detoxification of xenobiotics (Wikipedia, 2024). In many cancers, these enzymes are upregulated to provide a survival advantage and confer resistance to chemotherapy and radiation, making them attractive therapeutic targets (MDPI, 2024). Pharmacological modulation includes the use of inhibitors like buthionine sulfoximine (BSO) to deplete GSH or GPX4 inhibitors like RSL3 to trigger ferroptosis, as well as precursors like N-acetylcysteine (NAC) to replenish antioxidant capacity in neurodegenerative and inflammatory conditions (PubMed, 2021; NIH, 2026).

Other names

Glutathione metabolism enzymesGSH redox systemGlutathione systemGamma-glutamyl cycle enzymesThiol redox homeostasis enzymes

Inhibition of glutamate-cysteine ligase, inhibition of glutathione peroxidase 4, inhibition of glutathione reductase, glutathione precursor supplementation, glutathione peroxidase mimicry, induction of ferroptosis