Glutathione synthesis and cellular thiol-disulfide network (GSH/Thiol network)

The glutathione synthesis and cellular thiol-disulfide network is a fundamental biochemical system that maintains cellular redox homeostasis and protects against oxidative stress (Lu, 2013, PMID: 23517018). It centers on the production of glutathione (GSH), a tripeptide synthesized by glutamate-cysteine ligase (GCL) and glutathione synthetase (GSS), which serves as a major antioxidant and cofactor for enzymes like glutathione peroxidase (PubChem, 2024). The network also includes the thioredoxin and glutaredoxin systems, which utilize thiol-disulfide exchange to regulate protein activity, DNA synthesis, and signal transduction (Hanschmann et al., 2013, PMID: 23913832). In oncology, this network is frequently exploited by tumor cells to survive high oxidative loads, leading to the development of inhibitors like buthionine sulfoximine and erastin to induce ferroptosis or apoptosis (Dixon et al., 2012, PMID: 22624694). Conversely, in conditions like neurodegeneration and chronic inflammation, therapeutic strategies often aim to bolster this network using precursors like N-acetylcysteine to enhance cellular resilience against oxidative damage (Rushworth & Megson, 2014, PMID: 24835770). This integrated network is essential for balancing reactive oxygen species and maintaining the reduced state of critical protein thiols.

Other names

Glutathione metabolismRedox homeostasis systemThiol-disulfide exchange systemGSH-dependent antioxidant system

Modulation of cellular redox state through the regulation of glutathione synthesis, cystine uptake, or the activity of thiol-dependent enzymes like thioredoxin reductase and glutathione peroxidase (Lu, 2013; Dixon et al., 2012).