Figure 2: Glutathione homeostasis involves both intra- and extracellular mechanisms. Glutathione is synthesized in both de novo and salvage synthesis pathways. De novo synthesis requires the three amino acids and energy in the form of ATP. Glutamate may be provided in part from the conversion of a -glutamyl amino acid to 5-oxoproline, which is then converted to glutamate. Two ATP molecules are used for the biosynthesis of one GSH molecule. Salvage synthesis involves either reduction of GSSG or uses precursors formed from the hydrolysis of GSH or its conjugates by -L-glutamyl transpeptidase at the external surface of the plasma membrane that are transported back into the cell as amino acids or dipeptides. GSH is consumed in various processes. In addition to detoxification of reactive species and electrophiles such as methylglyoxal, GSH is involved in protein glutathionylation and several other processes, such as the biosynthesis of leukotrienes and prostaglandins, and reduction of ribonucleotides. Modified from [27].