MAMMALIAN GLUTATHIONE-S-TRANSFERASE - REGULATION OF AN ENZYME-SYSTEM TO ACHIEVE CHEMOTHERAPEUTIC EFFICACY

The glutathione S-transferases are a family of Phase II detoxication e nzymes that catalyze the conjugation of glutathione to a large variety of electrophilic compounds. In the 1990s, there have been many advanc es regarding the function of these enzymes in protecting a cell from t he toxic effects of these electrophiles. The complexity of this enzyme family has been realized and much work has been performed to identify the specific roles played by individual isozymes in resistance to a v ariety of agents. Likewise, the determination of the crystal structure of these enzymes has allowed the identification of specific amino, ac id residues that are involved in the catalysis of important reactions. The important role that these enzymes play in carcinogenesis and in d rug resistance has warranted an attempt to bring together these differ ent subfields of glutathione S-transferase biology to investigate poss ible ways that this system could be regulated in therapeutically usefu l ways. In this report, we have reviewed the recent advances and ways in which this knowledge could be utilized in the advancement of the tr eatment of cancer.