Gamma-glutamyl transpeptidase
Not to be confused with
GGGT.
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, the most notable one being the liver, and has significance in medicine as a diagnostic marker.
GGT[1] catalyzes the transfer of the gamma-glutamyl moiety of glutathione to an acceptor that may be an amino acid, a peptide or water (forming glutamate). GGT plays a key role in the gamma-glutamyl cycle, a pathway for the synthesis and degradation of glutathione and drug and xenobiotic detoxification.[2]
Function
GGT is present in the cell membranes of many tissues, including the kidneys, bile duct, pancreas, liver, spleen, heart, brain, and seminal vesicles.[3] It is involved in the transfer of amino acids across the cellular membrane[4] and leukotriene metabolism.[5] 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.[6][7] This general reaction is:
- (5-L-glutamyl)-peptide + an amino acid peptide + 5-L-glutamyl amino acid
Structural studies
In prokaryotes and eukaryotes, it is an enzyme that consists of two polypeptide chains, a heavy and a light subunit, processed from a single chain precursor by an autocatalytic cleavage. The active site of GGT is known to be located in the light subunit.
Medical applications
GGT has several uses as a diagnostic marker in medicine.
Blood test results for GGT suggest that the normal value for men is 15-85 IU/L, whereas for women it is 5-55 IU/L.[8]
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.[9][10] In general, 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.[10] More recently it has also been found to be elevated in persons with cardiovascular diseases and is under active investigation as a cardiovascular risk marker.
GGT is elevated by large quantities of alcohol ingestion.[11] Isolated elevation or disproportionate elevation compared to other liver enzymes (such as ALP or ALT) may indicate alcohol abuse or alcoholic liver disease.[12] 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.[13]
Numerous drugs can raise GGT levels, including barbiturates and phenytoin.[14] Others include NSAIDs, St. John's wort, and aspirin. Elevated levels of GGT may also be due to congestive heart failure.[15]
Human proteins
GGT1; GGT2; GGT6; GGTL3; GGTL4; GGTLA1; GGTLA4;
References
- ^ Tate SS, Meister A (1985). "gamma-Glutamyl transpeptidase from kidney". Meth. Enzymol. 113: 400–419. doi:10.1016/S0076-6879(85)13053-3. PMID 2868390.
- ^ Siest G, Courtay C, Oster T, Michelet F, Visvikis A, Diederich M, Wellman M (1992). "Gamma-glutamyltransferase: nucleotide sequence of the human pancreatic cDNA. Evidence for a ubiquitous gamma-glutamyltransferase polypeptide in human tissues". Biochem. Pharmacol. 43 (12): 2527–2533. doi:10.1016/0006-2952(92)90140-E. PMID 1378736.
- ^ Goldberg, DM (1980). "Structural, functional, and clinical aspects of gamma-glutamyltransferase". Crit Rev Clin Lab Sci 12 (1): 1–58. doi:10.3109/10408368009108725. 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. PMC 1453575. PMID 2860060. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1453575.
- ^ 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.
- ^ General Laboratory Manual. Department of Pathology, Hackensack University Medical Centre. 2010. p. 117. http://www.humc.com/lab_outreach/lab_services_10U.pdf. Retrieved 20 November 2011.
- ^ 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 (in Early identification of alcohol abuse). Biochemical basis for serum enzyme abnormalities in alcoholic liver disease. 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. doi:10.1002/hep.1840030308. 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.
- ^ Ruttmann, E; Brant, L; Concin, H; Diem, G; Rapp, K; Ulmer, H; Vorarlberg Health Monitoring and Promotion Program Study Group (2005). "Gamma-Glutamyltransferase as a Risk Factor for Cardiovascular Disease Mortality". Epidemiology 112 (14): 2130–2137. doi:10.1161/CIRCULATIONAHA.105.552547. PMID 16186419. http://circ.ahajournals.org/cgi/content/full/circulationaha;112/14/2130.
External links
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2.3.1: other than amino-acyl groups |
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2.3.2: Aminoacyltransferases |
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2.3.3: converted into alkyl on transfer |
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B enzm: 1.1/2/3/4/5/6/7/8/10/11/13/14/15-18, 2.1/2/3/4/5/6/7/8, 2.7.10, 2.7.11-12, 3.1/2/3/4/5/6/7, 3.1.3.48, 3.4.21/22/23/24, 4.1/2/3/4/5/6, 5.1/2/3/4/99, 6.1-3/4/5-6
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