Glutathione (gamma-glutamyl-cysteinyl-glycine; GSH) is the most abundant low-molecular-weight thiol in animal cells. The synthesis of GSH from glutamate, cysteine, and glycine is catalyzed sequentially by two cytosolic enzymes, gamma-glutamylcysteine synthetase and GSH synthetase. Specifically, GSH is synthesized in two adenosine triphosphate-dependent steps. First, gamma-glutamylcysteine is synthesized from L-glutamate and cysteine via the enzyme gamma-glutamylcysteine synthetase (GCL). Second, glycine is added to the C-terminal of gamma-glutamylcysteine via the enzyme glutathione synthetase. GSH synthesis is regulated primarily by gamma-glutamylcysteine synthetase activity, cysteine availability, and GSH feedback inhibition. Adequate protein nutrition is crucial for the maintenance of GSH homeostasis. Glutathione plays important roles in antioxidant defense, nutrient metabolism, and regulation of cellular events including gene expression, DNA and protein synthesis, cell proliferation, apoptosis, signal transduction, cytokine production and the immune response. Glutathione exists in reduced (GSH) and oxidized (GSSG) states. In the reduced state, the thiol group of cysteine is able to donate a reducing equivalent (H++ e-) to other unstable molecules, such as reactive oxygen species. In donating an electron, glutathione itself becomes reactive, but readily reacts with another reactive glutathione to form glutathione disulfide (GSSG). Such a reaction is possible due to the relatively high concentration of glutathione in cells (up to 5 mM in the liver). GSH can be regenerated from GSSG by the enzyme glutathione reductase.