Intracellular glutathione serves many roles in the cell including protection against oxidative damage caused by free radicals through glutathione peroxidase and detoxification of electrophilic metabolites through multiple glutathione transferases. Thereby, the level of glutathione in a specific organ or tissue is thought to be a major determinant of the vulnerability of that organ or tissue to oxidative stress. Although the majority of whole body glutathione is produced in hepatocytes, most cells, including the erythrocyte, have the equivalent capacity to synthesize glutathione de novo from the 3 amino acids cysteine, glutamate, and glycine utilizing (-glutamylcysteine and glutathione synthetases. The active form of glutathione (reduced or GSH) is also regenerated from recycling of oxidized glutathione (glutathione disulfide or GSSG) through glutathione reductase. However, when the use of reduced glutathione exceeds the capacity of regeneration, the GSSG is expelled from the cell and intracellular glutathione stores are depleted.