Glutathione and glutathione-dependent enzymes (GSH system)

Glutathione (GSH) is a tripeptide (gamma-L-glutamyl-L-cysteinylglycine) that serves as the primary endogenous antioxidant and a key player in cellular detoxification [1.2.2, 1.3.4]. The glutathione system includes several dependent enzymes, such as glutathione peroxidase (GPx), which reduces peroxides; glutathione S-transferase (GST), which conjugates toxins; and glutathione reductase (GR), which regenerates GSH from its oxidized form (GSSG) [1.2.3, 1.3.3]. This system is critical for maintaining redox homeostasis and protecting cells from oxidative damage and electrophilic stress [1.4.1, 1.4.2]. In disease, dysregulation of the glutathione system is linked to neurodegeneration, liver disorders, and cancer [1.3.2, 1.4.1]. In oncology, elevated GSH levels often contribute to chemotherapy resistance by neutralizing drugs or preventing apoptosis [1.3.1, 1.4.3]. Therapeutic strategies involve either depleting GSH to sensitize tumors, such as using buthionine sulfoximine (BSO), or supplementing precursors like N-acetylcysteine (NAC) to bolster antioxidant defenses [1.3.4, 1.4.3]. Additionally, GST inhibitors like ezatiostat are being explored to modulate cell signaling and overcome drug resistance [1.4.2]. Monitoring the GSH/GSSG ratio and specific enzyme activities serves as a valuable biomarker for assessing cellular oxidative stress and therapeutic efficacy [1.3.2, 1.3.3].

Other names

Glutathione systemGSH-dependent enzymesGlutathione-associated metabolismGSH redox system

Inhibition of glutamate-cysteine ligase (GCL); inhibition of glutathione S-transferase (GST); supplementation of glutathione precursors; mimicry of glutathione peroxidase (GPx) activity; direct antioxidant scavenging [1.3.4, 1.4.2, 1.4.3].