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 initiates the cleavage of extracellular glutathione into its constituent amino acids which can then be transported into the cell. It also catalyzes the initial step in the conversion of glutathione-conjugated compounds to mercapturic acids. GGT is expressed at high levels in many human tumors and in many carcinogen-induced tumors in animals. These observations have lead an increased focus on the role of the enzyme in the development and treatment of tumors. This chapter begins with an overview of the structure and function of GGT in normal tissues. A summary of its expression in neoplastic tissues and the ways in which GGT effects the response of tumors to chemotherapy follows. The chapter concludes with a discussion of strategies for using GGT to activate and target chemotherapy drugs to tumors as a means of improving treatment for common human malignancies.