Gamma-glutamyltransferase or gamma-glutamyl transpeptidase (also γ-glutamyltransferase, GGT, GGTP, gamma-GT) (EC 2.3.2.2) is an enzyme that transfers gamma-glutamyl functional groups. It is found in many tissues, most notably the liver, and has significance in medicine as a diagnostic marker.
Function
GGT is present in the cell membranes of many tissues, including the kidneys, bile duct, pancreas, liver, spleen, heart, brain, and seminal vesicles.[1] It is involved in the transfer of amino acids across the cellular membrane[2] and leukotriene metabolism.[3] It is also involved in glutathione metabolism by transferring the glutamyl moiety to a variety of acceptor molecules including water, certain L-amino acids, and peptides, leaving the cysteine product to preserve intracellular homeostasis of oxidative stress.[4][5] This general reaction is:
- (5-L-glutamyl)-peptide + an amino acid
peptide + 5-L-glutamyl amino acid
Structural studies
As of late 2007, 8 structures have been solved for this class of enzymes, with PDB accession codes 2DBU, 2DBW, 2DBX, 2DG5, 2E0W, 2E0X, 2E0Y, and 2NQO.
Medical applications
GGT has several uses as a diagnostic marker in medicine.
Elevated serum GGT activity can be found in diseases of the liver, biliary system, and pancreas. In this respect, it is similar to alkaline phosphatase (ALP) in detecting disease of the biliary tract. Indeed, the two markers correlate well, though there is conflicting data about whether GGT has better sensitivity.[6][7] Generally, ALP is still the first test for biliary disease. The main value of GGT over ALP is in verifying that ALP elevations are in fact due to biliary disease; ALP can also be increased in certain bone diseases, but GGT is not.[7]
GGT is elevated by large quantities of alcohol ingestion.[8] Isolated elevation or disproportionate elevation compared to other liver enzymes (such as ALP or ALT) may indicate alcohol abuse or alcoholic liver disease.[9] It may indicate excess alcohol consumption up to 3 or 4 weeks prior to the test. The mechanism for this elevation is unclear. Alcohol may increase GGT production by inducing hepatic microsomal production, or it may cause the leakage of GGT from hepatocytes.[10]
Numerous drugs can raise GGT levels, including barbiturates and phenytoin.[11] Others include NSAIDs, St. John's wort, and aspirin.[citation needed] Elevated levels of GGT may also be due to congestive heart failure.[citation needed]
References
- ^ Goldberg, DM (1980). "Structural, functional, and clinical aspects of gamma-glutamyltransferase". Crit Rev Clin Lab Sci 12 (1): 1-58. PMID 6104563.
- ^ Meister A (August 1974). "The gamma-glutamyl cycle. Diseases associated with specific enzyme deficiencies". Ann. Intern. Med. 81 (2): 247–53. PMID 4152527.
- ^ Raulf M, Stüning M, König W (May 1985). "Metabolism of leukotrienes by L-gamma-glutamyl-transpeptidase and dipeptidase from human polymorphonuclear granulocytes". Immunology 55 (1): 135–47. PMID 2860060.
- ^ Schulman JD, Goodman SI, Mace JW, Patrick AD, Tietze F, Butler EJ (July 1975). "Glutathionuria: inborn error of metabolism due to tissue deficiency of gamma-glutamyl transpeptidase". Biochem. Biophys. Res. Commun. 65 (1): 68–74. doi:10.1016/S0006-291X(75)80062-3. PMID 238530.
- ^ Yokoyama H (June 2007). "[Gamma glutamyl transpeptidase (gammaGTP) in the era of metabolic syndrome]" (in Japanese). Nihon Arukoru Yakubutsu Igakkai Zasshi 42 (3): 110–24. PMID 17665541.
- ^ Betro MG, Oon RC, Edwards JB (November 1973). "Gamma-glutamyl transpeptidase in diseases of the liver and bone". Am. J. Clin. Pathol. 60 (5): 672–8. PMID 4148049.
- ^ a b Lum G, Gambino SR (April 1972). "Serum gamma-glutamyl transpeptidase activity as an indicator of disease of liver, pancreas, or bone". Clin. Chem. 18 (4): 358–62. PMID 5012259.
- ^ Lamy, J; Baglin, MC; Ferrant, JP; Weill, J (1974). "Determination de la gamma-glutamyl transpeptidase senque des ethyliques a la suite du sevrage". Clin Chim Acta 56: 169.
- ^ Kaplan, MM; et al (1985), Chang, NC; Chan, NM, ed., "Biochemical basis for serum enzyme abnormalities in alcoholic liver disease" (in Early identification of alcohol abuse), Research Monograph No. 17 (NIAAA): p. 186
- ^ Barouki R; Chobert MN; Finidori J; Aggerbeck M; Nalpas B; Hanoune J (May-Jun 1983). "Ethanol effects in a rat hepatoma cell line: induction of gamma-glutamyltransferase". Hepatology 3 (3): 323-9. PMID 6132864.
- ^ Rosalki SB, Tarlow D, Rau D (August 1971). "Plasma gamma-glutamyl transpeptidase elevation in patients receiving enzyme-inducing drugs". Lancet 2 (7720): 376–7. PMID 4105075.
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