Increase In Gamma-glutamyl Transpeptidase Activity Research Articles

Enzyme histochemical studies on transplantable pancreatic adenocarcinomas in Syrian golden hamsters

Transplantable pancreatic adenocarcinomas were established in subcutaneous tissue of Syrian golden hamsters and examined by enzyme histochemistry. The original tumors were found at week 40 after subcutaneous injection of N-nitrosobis(2-hydroxypropyl)amine (DHPN) at a dose of 250 mg/kg body weight once a week for the first 20 weeks of the experiment. They were well differentiated adenocarcinomas and their histology was not changed by serial transfer for 18 generations. Their transplantability was 67 to 100% and their average doubling time was 4.1 +/- 0.82 d. The enzymes gamma-glutamyl transpeptidase (GGT), lactate dehydrogenase (LDH), succinate dehydrogenase (SDH), alkaline phosphatase (ALPase), and acid phosphatase (ACPase) were examined in tumor cells at the 14th and 15th generations and in ductal cells and acinar cells of normal pancreas of hamsters. Increased GGT activity was found in the tumor cells, and a strongly positive reaction was observed in acinar cells but not ductal cells of normal pancreas. LDH and SDH were found in the tumor cells, acinar cells and ductal cells. No ALPase was detected in the tumor cells, acinar cells, or ductal cells. ACPase was found in acinar cells and ductal cells, but not in the tumor cells.

Transport of amino acids in gamma-glutamyl transpeptidase-implanted human erythrocytes.

gamma-Glutamyl transpeptidase purified from hog kidney cortex was implanted in the human erythrocyte membrane by incubation of erythrocytes at 37 degrees c with gamma-glutamyl transpeptidase-incorporated dipalmitoyl phosphatidylcholine vesicles. Membranes prepared from these implanted cells exhibited 4- to 5-fold increase in gamma-glutamyl transpeptidase activity. The association/insertion of gamma-glutamyl transpeptidase into erythrocyte membrane was further demonstrated by antibody to gamma-glutamyl transpeptidase. Implantation of gamma-glutamyl transpeptidase into erythrocyte membrane led to stimulation of uptake of glutamate and alanine, which are normally transported at a slow rate in human erythrocytes. The uptake of these amino acids in the implanted system was inhibited by inhibitors (serine-borate and azaserine) of transpeptidase activity as well as by antibody to gamma-glutamyl transpeptidase. These results in the implanted human erythrocytes demonstrate that gamma-glutamyl transpeptidase enzyme can mediate the translocation of amino acids and provide further evidence in support of its postulated role in the transport of amino acids in natural membranes.

Developmental formation and cortisol regulation of gamma-glutamyl transpeptidase in brain and spinal cord of chick embryo.

The developmentally conditioned changes in gamma-glutamyl transpeptidase (GGT) activity in chick embryonic hemispheres, optic lobes, cerebellum, brain stem and in lumbar and brachial enlargements of the spinal cord were studied. A marked increase in GGT activity was found in all tissues between embryonic day 11 and hatching. The application of cortisol enhanced GGT activity particularly on embryonic days 15 and 17. This effect of cortisol was reversed by the concomitant administration of actinomycin D or cycloheximide. The results are discussed in relation to the potential metabolic and transport role of GGT and its regulation in the developing chick embryonic brain.

Peptidase activities in the functioning jejunum and ileum before and after jejunoileal bypass in morbid obesity.

Different peptidase activities were studied preoperatively and postoperatively on intestinal biopsy specimens from patients with jejunoileal bypass for morbid obesity. Preoperatively the activities of the brush border peptidases, microvillus aminopeptidase (EC 3.4.11.2) and dipeptidyl peptidase IV (EC 3.4.14.X), were lowest at the ligament of Treitz and highest in the distal ileum. The activity of the other brush border peptidase studied, the gamma-glutamyl transpeptidase (EC 2.3.2.2), had a maximum at proximal jejunum, like the two cytosol dipeptidases glycyl-leucine dipeptidase (EC 3.4.13.2) and proline dipeptidase (EC 3.4.13.9). Postoperative changes in peptidase activities were most pronounced in the ileal part of the shunt, whereas changes were small in the jejunal part. The most conspicuous finding was a significant increase in gamma-glutamyl transpeptidase activity in the ileum. There was also tendency to an increase of the cytosol dipeptidases in the ileum. In contrast, the activity of microvillus aminopeptidase and dipeptidyl peptidase IV in the ileum had a tendency to decrease.

Serum gamma-glutamyl transpeptidase activity and urinary D-glucaric acid excretion in newborns in the first week of life. Effects of phenobarbital and nicethamide combination.

High serum gamma-glutamyl transpeptidase activity was found in cord blood of newborn boys. This activity decreased to lower values on the 4th and 7th days. In newborns treated for 3 days following the birth with a combination of phenobarbital and nicethamide an increase of gamma-glutamyl transpeptidase activity occurred from the 4th to the 7th days. The 7th day levels were significantly higher when compared with the controls. Simultaneous determination of urinary glucaric acid excretion confirmed the induction of hepatic microsomal enzymes in glucuronic acid pathway. This could also be demonstrated by a pronounced decrease of serum bilirubin levels in groups receiving the enzyme inducers whether phenobarbital was administered intramuscularly or orally as sodium salt solution.

Glutathione and gamma-glutamyl cycle enzymes in crypt and villus tip cells of rat jejunal mucosa.

Villus tip cells and crypt cells of rat jejunal mucosa were separated by the planning procedure of Imondi et al. and were studied with respect to their activities of the enzymes of the gamma-glutamyl cycle and glutathione content. The villus tip cells exhibit much higher gamma-glutamyl transpeptidase activities than do the crypt cells: thus, gamma-glutamyl trnaspeptidase appears to be a villus-specific enzyme. gamma-Glutamyl cyclotransferase and the enzymes required for glutathione synthesis are not specifically localized to either the crypt or villus tip cells but are present in both. The crypt cells have a high concentration of glutathione (4-5 mM) comparable to the levels found in liver and kidney; in contrast, the villus tip cells have much lower concentrations. On fasting, the glutathione concentration decreased markedly in both villus tip and crypt cells; feeding of protein, but not of sucrose, led to increased glutathione concentrations. The migration of cells from the undifferentiated crypt cell region to the villus tip is associated with structural and biochemical changes that equip the cell for its mature functional activities, which include transport. The present findings indicate that such cellular differentiation and migration is associated with a marked increase in gamma-glutamyl transpeptidase activity and in the utilization of glutathione.