Glutathione metabolism system proteins (GSH system)

The glutathione metabolism system consists of a complex network of redox-sensitive proteins and enzymes that maintain cellular thiol redox homeostasis and protect cells from oxidative damage (Source: PMID: 23911665). Key components include Glutamate-cysteine ligase (GCL), the rate-limiting enzyme for glutathione (GSH) synthesis, and Glutathione peroxidases (GPx), which utilize GSH to neutralize reactive oxygen species and lipid hydroperoxides (Source: UniProt P18283, P36969). This system is also integral to the detoxification of xenobiotics via Glutathione S-transferases (GST) and the regulation of ferroptosis, a lipid peroxidation-driven form of cell death (Source: PMID: 32213333). In many cancers, these proteins are upregulated to provide a survival advantage and resistance against pro-oxidant therapies like radiation and chemotherapy (Source: PMID: 24484021). Conversely, deficiencies in this system are linked to neurodegenerative conditions such as Parkinson's disease, where oxidative stress leads to neuronal loss (Source: NIH/NINDS). Therapeutic strategies include the use of Buthionine sulfoximine (BSO) to deplete GSH in tumors or N-acetylcysteine (NAC) to replenish GSH levels in respiratory and toxicological conditions (Source: PubChem CID 5462224, 12035). Because this entry refers to a broad system of proteins rather than a single molecular entity, it is classified as a collective target group.

Other names

Glutathione redox systemGSH-dependent antioxidant systemGlutathione metabolic pathwayRedox-sensitive glutathione proteins

Modulation of intracellular glutathione levels through the inhibition of rate-limiting synthetic enzymes, blockade of cystine transport, or direct mimicry of antioxidant enzyme activity to alter cellular redox potential and sensitivity to oxidative stress-induced death.