Structural, Functional, and Clinical Aspects of γ-Glutamyltransferase

Abstract

GGT catalyses the transfer of gamma-glutamyl residues to amino acids or small peptides. A number of publications report the purification of GGT, the rat kidney enzyme being the best characterized. Bromelain treatment liberates an active form with a molecular weight of 68,000 separable into two nonidentical glycopeptides with molecular weights of 46,000 and 22,000; the latter contains the gamma-glutamyl binding site. GGT is intimately concerned in the synthesis and metabolism of glutathione through the gamma-glutamyl cycle. There is good evidence that this plays a role in the absorption of amino acids from the glomerular filtrate and from the intestinal lumen through a translocation mechanism. Many studies indicate that the GGT content of liver is increased by enzyme-inducing drugs and that this increase is reflected in elevated activity of the enzyme in blood serum. The serum assay has potential in monitoring drug compliance. Increased serum GGT activity encountered in chronic alcoholics seems to be partly due to microsomal enzyme induction. Utility of the assay in detecting alcoholism is controversial, but it is a useful index to compliance with therapy. Dramatic increases in activity are found in many chemically-induced animal tumors, and can be recognized in premalignant cells long before any morphological changes become evident. It has been used as a test for hepatic metastases, but its predictive value has shown a wide range in the hands of many authors. A similar controversy applies to its role in monitoring cancer therapy. Many synthetic substrates have been used to measure serum GGT activity. Currently, L-gamma-glutamyl-p-nitroanilide is the most popular. Males have higher values than females; activity is very high in the neonate and rather low in pregnancy. The most universal application of serum GGT assay is in diagnosis of liver and biliary tract disease. It is widely believed that higher values occur in biliary obstruction than in parenchymal disease. However, the percentage incidence of abnormalities and the overlap of values in individual cases in different disease categories are so great that the enzyme cannot be recommended for this purpose. Isoenzyme analyses have been performed in an attempt to improve the diagnostic specificity of the serum GGT assay. Tissue-specific patterns have not been described, and disease-specific patterns cannot be reproduced with confidence. Whereas exciting advances are being made in understanding the molecular structure, mechanism, and functions of the enzyme it has yet to find a genuinely useful diagnostic role substantiated by a convincing body of scientific data.

Can persistent organic pollutants explain the association between serum γ-glutamyltransferase and type 2 diabetes?

“…A similar pattern of associations was observed in datasets from the Coronary Artery Risk Development in Young Adults (CARDIA) study [2], the Finland Multinational Monitoring of Trends and Determinants in Cardiovascular Disease (FinMONICA) study [3], the National Health and Nutrition Examination Survey (NHANES) [4], and in German women, but not men [5], leading us to search for new interpretations of serum GGT. Cellular GGT, found on the plasma membrane in most tissues [6], metabolises extracellular glutathione (GSH), the main intracellular antioxidant, allowing precursor amino acids to be reutilised for intracellular GSH re-synthesis [7]a process known as the 'γ-glutamyl cycle' (Fig. 1, left of the dotted line) [8].…”

Gamma Glutamyltransferase and Long-Term Survival: Is It Just the Liver?

“…Serum GGT is significantly increased in hepatobiliary diseases, with highest concentrations in cholestatic conditions (1,3 ).…”

“…The glycoprotein gamma glutamyltransferase (GGT) 4 is located on membranes of cells with high secretory or absorptive activities, such as in liver, kidney, pancreas, intestine, heart, brain, and prostate, but not in bone or erythrocytes (1,2 ). Serum GGT is significantly increased in hepatobiliary diseases, with highest concentrations in cholestatic conditions (1,3 ).…”

Evaluation of Hypolipidemic and Hepatoprotective Effects of Ethanolic Extract of Cleome Brachycarpa on Albino Rabbits

“…ALP levels elevate in infiltrative diseases of liver. Gamma GT is present in cell membranes of many tissues of bile duct, gall bladder, heart, brain and kidney etc [37].…”