glycine to glutamyl-cysteine to form glutathione (?-glutamyl-cysteinyl-glycine). More than 98% of total glutathione is present as GSH and the rest is found as the oxidised form, glutathione disulfide (GSSG) or a range of glutathione-S-conjugates. GSH is readily converted to GSSG by the seleno-enzyme glutathione peroxidase (GPx) during periods of oxidative stress, and is reverted to the reduced form by glutathione reductase (GSH-R) [ 35 ]. GSH is also important in detoxification as it is used to conjugate a wide variety of exogenous compounds including carcinogens, toxins and drugs and endogenous electrophiles. The glutathione conjugate is subsequently secreted from the cell [ 36 ]. Glutathione degradation takes place in the extracellular space. Cysteine is released from extracellular glutathione by ?-glutamyl-transferase (GGT) located on the apical surface of the kidney, intestine and the epithelia of most transporting ducts, including the liver and bile ducts [ 37 ]. Expression of GGT is tissue and developmental stage specific and its activity may be induced by certain xenobiotics [ 37 ]. GGT hydrolyses the ?-glutamyl bond of glutathione or glutathione-S-conjugates and transfers the ?-glutamyl moiety to an acceptor molecule, often an amino acid [ 38 ]. If the substrate is glutathione, cysteinyl-glycine is released and subsequently cleaved into cysteine and glycine by cell surface dipeptidases. The ?-glutamyl amino acid can be transported back into the cell where ?-glutamyl cyclo-transferase (GCT) releases the acceptor amino acid to form 5-oxo-proline, the latter of which is converted back to glutamate by oxo-prolinase and used for GSH synthesis. About