Glutathione system (GSH system) (GSH system)

The glutathione system is a fundamental cellular defense network comprising the tripeptide glutathione (GSH) and several key enzymes, including glutathione peroxidases (GPx), glutathione reductases (GR), and glutathione S-transferases (GST) [2, 6, 23]. Its primary role is maintaining cellular redox homeostasis by neutralizing reactive oxygen species and detoxifying a wide range of endogenous and exogenous electrophiles through Phase II conjugation [2, 7, 23]. In oncology, the system is frequently exploited by tumor cells, which overexpress GSTs to deactivate chemotherapeutic drugs, leading to multi-drug resistance [1, 12, 13]. Conversely, a deficiency in the glutathione system is linked to neurodegenerative diseases, chronic inflammation, and viral infections, where oxidative stress predominates [6, 9, 11]. Therapeutic interventions include the use of GSH precursors like N-acetylcysteine to replenish cellular stores, GST inhibitors like ethacrynic acid to sensitize cancer cells, and Nrf2 activators to enhance the overall antioxidant response [1, 9, 11, 12]. However, targeting this system carries risks, as profound GSH depletion can trigger severe organ damage, and exogenous administration has been linked to rare but serious adverse reactions like anaphylaxis [14, 15, 16].

Other names

Glutathione system and related enzymesGlutathione antioxidant systemGSH-related enzymesGlutathione metabolic pathwayMeister cycle

Modulation of cellular redox state and detoxification capacity through enzyme inhibition (e.g., GST, GCL), substrate supplementation (e.g., NAC, GSH), or transcriptional activation of the Nrf2 pathway [1, 9, 11, 12, 23].