FIG. 2.

GSH-related enzymes. GSH synthesis: First, γ-glutamylcysteine is synthesized from L-glutamate and cysteine via the enzyme GCL, containing GCLC and GCLM subunits. Second, glycine is added to the C-terminal of glu-cys via the enzyme GS. GSH exists in two forms: reduced (GSH) and oxidized (GSSG). In the reduced state, the thiol group of cysteine is able to donate an electron to other unstable molecules, such as ROS to form H₂O₂, or it may readily react with another GSH to form glutathione disulfide (GSSG). Gpx catalyzes the GSH-dependent reduction of H₂O₂ to harmless H₂O. GSH can be regenerated from GSSG by the NADPH-dependent enzyme glutathione reductase (Gr). GSH also reacts with various electrophiles, physiological metabolites, and xenobiotics. These reactions are initiated by GST where GSH serves as a cofactor in conjugation reactions to form a glutathione S-conjugate (GSX).