The inhibition of glutathione S-transferases: mechanisms, toxic consequences and therapeutic benefits.

Inhibition of the enzymes belonging to the family of glutathione S-transferases is important from several points of view. These involve applications in studies of the catalytic mechanism, e.g. studying the topology and binding characteristics of the active site. Also, from a therapeutic standpoint, inhibition of glutathione S-transferases steadily becomes more interesting, since these enzymes appear to be involved in drug resistance, and in the biosynthesis of a number of important arachidonic acid metabolites such as prostaglandins and leukotrienes. Modulation of the glutathione S-transferase activity could be used to regulate the concentrations of these compounds, Thirdly, unwanted inhibition by xenobiotics makes a cell more vulnerable for alkylating agents and can thus have toxic consequences. This review describes the state of the art, dealing with the various types of inhibiton employed (reversible, irreversible or nonsubstrate ligands). Furthermore, isoenzyme selectivity, organ distribution and interindividual differences are discussed.