Glutathione synthesis pathway via cysteine supply

The "Glutathione synthesis pathway via cysteine supply" is not a single molecular target but rather describes the **metabolic process** by which cells synthesize the tripeptide antioxidant **glutathione** using **L-cysteine** as an essential precursor. The rate-limiting step in this process is catalyzed by the enzyme **glutamate–cysteine ligase**, which combines L-glutamate with L-cysteine to form γ-glutamylcysteine. This intermediate then reacts with glycine via **glutathione synthetase** to produce reduced glutathione (GSH)[5]. The availability of L-cysteine is often the limiting factor for cellular GSH production—dietary intake and metabolic pathways that generate free cysteine are therefore critical regulators. Dysregulation in this pathway contributes significantly to diseases involving oxidative stress, including cancer progression/resistance, diabetes complications, fibrotic diseases, liver injury, and immune dysfunctions. Pharmacological agents can modulate this pathway either by supplying precursors like N-acetylcysteine or targeting regulatory enzymes directly.[1][2][4][5] Because this entry refers broadly to a biochemical process rather than an individual druggable entity such as an enzyme or receptor—and because it lacks specificity regarding which component is being targeted—it should be flagged as "not a canonical therapeutic target" per standard conventions.

Other names

Glutathione biosynthesis (via cysteine)GSH synthesis pathway (cysteine-dependent)Cysteine-dependent glutathione synthesisγ-glutamyl cycle (partial, when referring to cysteine supply)

Drugs may act by increasing the supply of cysteine (precursor), inducing expression or activity of key enzymes such as glutamate–cysteine ligase or glutathione synthetase, or inhibiting these enzymes to deplete cellular GSH levels.[4][5]