Studies on the Mechanisms of Serum Gamma-Glutamyl Transpeptidase Elevation in Hepatobiliary Disorders

Abstract

With a view to elucidate the underlying mechanisms of serum γ-glutamyl transpeptidase (γ-GTP) elevation in various clinical hepatobiliary diseases, the characteristics of the activity changes in serum and hepatic γ-GTP were studied on rats with experimental models of liver injuries. γ-GTP in the liver was localized mainly in the microsomal fraction of the parenchymal cells and was gradually induced in the course of chronic liver injury with a consequent rise in the serum activity, whereas in acute liver damage, both serum and hepatic γ-GTP levels remained within the normal limits. On ligation of the common bile duct, the activity of serum γ-GTP was elevated with consistently normal concentration of the hepatic enzyme, thus suggesting that the enzyme is normally excreted into intestine via biliary system. Neither serum γ-GTP nor the hepatic enzyme activity was elevated in rats with regenerating liver or fatty liver. Morris' hepatoma-bearing rats showed a marked increase in serum γ-GTP as well as in the particle-bound enzyme in the implanted tumor cells whilst the enzyme in the host liver remained within the normal limits, thereby indicating the rise in serum γ-GTP activity to be derived from tumor cells. In the alcoholic liver γ-GTP showed dose-related increase in some extent, while with dosage over 6gm/kg the specific activity of the hepatic enzyme diminished without any significant alteration in the serum activity.