Structural, functional, and clinical aspects of gamma-glutamyltransferase - PubMed (original) (raw)

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Structural, functional, and clinical aspects of gamma-glutamyltransferase

D M Goldberg. CRC Crit Rev Clin Lab Sci. 1980.

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.

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