The Glutathione Transferases in Detoxification

Summary

The glutathione transferases (EC 2.5.1.18) appear to perform several detoxification functions. This group of enzvmes is analogous to serum albumin in the broad spectrum of compounds that serve as ligands, but differs significantly in that the transferases have an additional and specific site for GSH. They appear to catalyze all reactions that would be expected of GSH acting as a nucleophile, providing that the electro-philic substrate is bound to the enzyme. Examples of the reactions catalyzed include conjugation to compounds with a reactive electrophilic carbon to form thioethers; reactions with other electrophilic atoms including the nitrogen of organic nitrates and the sulfur of organic thiocyanates; isomerization; disulfide interchange; glutathione peroxidase activity with organic peroxides; and the formation of a thiolester from p-nitrophenylacetate.

The enzymes have been shown to act as storage proteins and appear to be responsible for the binding of bilirubin and its conjugates, among many other compounds, within the hepatocyte. A more speculative scavenger function has also been suggested for them.

These enzymes are widely distributed in higher animals and constitute 10% and 3%, respectively, of the extractable protein of rat and human liver.