Gene expression of gamma-glutamyltranspeptidase.

gamma-Glutamyltranspeptidase is a heterodimeric glycoprotein that catalyzes the transpeptidation and hydrolysis of the gamma-glutamyl group of glutathione and related compounds. It is known that the enzyme plays a role in the metabolism of glutathione and in salvaging constituents of glutathione. In the adult animal, high levels of gamma-glutamyltranspeptidase are constitutively expressed in the kidney, intestine, and epididymis. On the other hand, although gamma-glutamyltranspeptidase is up-regulated in the liver during the perinatal stage, its expression is nearly undetectable in the adult. In addition, it has long been observed that the intake of certain xenobiotics, including carcinogens and drugs, induces the hepatic expression of the enzyme. This induction seems to be associated with both transcriptional regulation and the growth of certain types of cells in the injured liver. A number of studies have been carried out to explain the mechanism by which gamma-glutamyltranspeptidase expression is regulated. 5'-Untranslated regions of mRNAs of the enzyme differ in a tissue-specific manner but share a common protein coding region, and the tissue-specific and developmental stage-specific expression, as well as hepatic induction, are conferred by different promoters. As suggested by the capability of enzymatic activity-independent induction of osteoclasts, the expression of gamma-glutamyltranspeptidase may also be involved in various biological processes that are not directly associated with glutathione metabolism. This chapter briefly summarizes studies to date concerning the tissue-specific expression and induction of gamma-glutamyltranspeptidase and transcriptional regulation by the multiple promoter system is discussed.