GAMMA-GLUTAMYL-TRANSPEPTIDASE, A GLUTATHIONASE - ITS EXPRESSION AND FUNCTION IN CARCINOGENESIS

gamma-Glutamyl transpeptidase (GGT) is found throughout the plant and animal kingdoms. It is a cell surface glycoprotein that cleaves gamma- glutamyl amide bonds. The most abundant physiologic substrates for the enzyme are glutathione and glutathione-conjugated compounds. GGT init iates the cleavage of extracellular glutathione into its constituent a mino acids which can then be transported into the cell. It also cataly zes the initial step in the conversion of glutathione-conjugated compo unds to mercapturic acids. GGT is expressed at high levels in many hum an tumors and in many carcinogen-induced tumors in animals. These obse rvations have lead an increased focus on the role of the enzyme in the development and treatment of tumors. This chapter begins with an over view of the structure and function of GGT in normal tissues. A summary of its expression in neoplastic tissues and the ways in which GGT eff ects the response of tumors to chemotherapy follows. The chapter concl udes with a discussion of strategies for using GGT to activate and tar get chemotherapy drugs to tumors as a means of improving treatment for common human malignancies. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.