Glutathione (intracellular glutathione) (GSH)

**Glutathione** is a tripeptide composed of glutamate, cysteine, and glycine, and is the most abundant intracellular non-protein thiol. It acts as a major antioxidant, maintaining redox balance, detoxifying xenobiotics, and participating in a variety of cell signaling, metabolic, and protective processes[1][2][3][6][8]. The term "intracellular glutathione level" refers to a quantitative cellular state rather than a discrete molecular target, such as a receptor, enzyme, or channel. Cellular GSH is synthesized de novo (catalyzed by glutamate-cysteine ligase and glutathione synthase), consumed in redox and conjugation reactions, and recycled from its oxidized form (GSSG) by glutathione reductase[2][3][4][5]. Abnormal GSH levels are implicated in a wide range of diseases including cancer, neurodegeneration, cardiovascular dysfunction, and chronic inflammation[9]. Drugs may modulate GSH levels directly (by providing precursors or inhibitors) or indirectly (by affecting redox state or GSH-consuming reactions). Measurement of GSH or the GSH/GSSG ratio is commonly used in research and clinical settings as a biomarker of oxidative status[5][9]. **Note:** - "Intracellular glutathione level" is not a canonical single target (e.g., receptor or enzyme), but a physiological or biochemical parameter. Therefore, is_target = false; is_incorrect = true as it is not an individual molecule/receptor but a measurable property of GSH within cells. - The correct molecular target for intervention would usually be an enzyme of GSH metabolism (e.g., glutamate-cysteine ligase, glutathione reductase) or GSH itself. **Further information:** - Mechanistically, drugs such as N-acetylcysteine act as GSH precursors, elevating intracellular levels, while buthionine sulfoximine inhibits synthesis, leading to depletion[1][5]. - Depletion of GSH can sensitize cells to oxidative stress and cytotoxicity, while elevated levels are linked to drug resistance and tumor cell survival[7][8][9].

Other names

Intracellular GSHReduced glutathioneγ-L-glutamyl-L-cysteinyl-glycine

Redox modulation; Free radical scavenging; Conjugation with electrophiles