The glutathione S-transferases: a group of multifunctional detoxification proteins

Abstract

The physiological roles of the glutathione S-transferases, by whatever name, seem to result in detoxification. As is true of albumin, members of this group of proteins bind an enormous number of compounds that appear to have in common only hydrophobic topography; the binding of bilirubin is an example of a major function common to all higher species. If the ligand bears a sufficiently electrophilic center, it will be attacked by the nucleophile GSH; such compounds would be the substrates of the enzyme. And should such a ligand be extraordinarily reactive--as, for example, some of the epoxide carcinogens generated by the cytochrome P450-linked, mixed-function oxidases, or even 1-chloro-2,4-dinitrobenzene--then reaction may occur either with GSH or irreversibly with the transferase itself. By reason of the wide distribution and high intracellular concentration of these proteins, there appears to be sufficient enzyme for all three roles in detoxification.