Gamma-glutamyl transpeptidase

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Gamma-glutamyltranspeptidase
Identifiers
Symbol G_glu_transpept
Pfam PF01019
InterPro IPR000101
PROSITE PDOC00404
gamma-glutamyltransferase
Identifiers
EC number 2.3.2.2
CAS number 9046-27-9
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Gene Ontology AmiGO / EGO
gamma-glutamyltransferase 1
Identifiers
Symbol GGT1
Alt. symbols GGT
Entrez 2678
HUGO 4250
OMIM 231950
RefSeq NM_001032364
UniProt P19440
Other data
EC number 2.3.2.2
Locus Chr. 22 q11.1-11.2
gamma-glutamyltransferase 2
Identifiers
Symbol GGT2
Alt. symbols GGT
Entrez 2679
HUGO 4251
OMIM 137181
RefSeq NM_002058
UniProt P36268
Other data
EC number 2.3.2.2
Locus Chr. 22 q11.1-11.2

Gamma-glutamyl transferase or gamma-glutamyl transpeptidase (also γ-glutamyl transferase, GGT, GGTP, gamma-GT) (EC 2.3.2.2) is an enzyme that transfers gamma-glutamyl functional groups. This transferase 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] Other lines of evidence indicate that GGT can also exert a prooxidant role, with regulatory effects at various levels in cellular signal transduction and cellular pathophysiology.[3]

Function[edit]

GGT is present in the cell membranes of many tissues, including the kidneys, bile duct, pancreas, gallbladder, spleen, heart, brain, and seminal vesicles.[4] It is involved in the transfer of amino acids across the cellular membrane[5] and leukotriene metabolism.[6] 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.[7][8] This general reaction is:

(5-L-glutamyl)-peptide + an amino acid peptide + 5-L-glutamyl amino acid

Structural studies[edit]

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[edit]

GGT is predominantly used as a diagnostic marker for liver disease. Latent elevations in GGT are typically seen in patients with chronic viral hepatitis infections often taking 12 months or more to present.

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, slightly elevated serum GGT has also been found to correlate with cardiovascular diseases and is under active investigation as a cardiovascular risk marker. GGT in fact accumulates in atherosclerotic plaques,[11] suggesting a potential role in pathogenesis of cardiovascular diseases,[12] and circulates in blood in the form of distinct protein aggregates,[13] some of which appear to be related to specific pathologies such as metabolic syndrome, alcohol addiction and chronic liver disease. High body mass index is associated with type 2 diabetes only in persons with high serum GGT.[14]

GGT is elevated by ingestion of large quantities of alcohol. However, determination of high levels of total serum GGT activity is not specific to alcohol intoxication,[15] and the measurement of selected serum forms of the enzyme offer more specific information.[13] Isolated elevation or disproportionate elevation compared to other liver enzymes (such as ALP or alanine transaminase) can indicate alcohol abuse or alcoholic liver disease,[16] and can indicate excess alcohol consumption up to 3 or 4 weeks prior to the test. The mechanism for this elevation is unclear. Alcohol might increase GGT production by inducing hepatic microsomal production, or it might cause the leakage of GGT from hepatocytes.[17]

Numerous drugs can raise GGT levels, including barbiturates and phenytoin.[18] GGT elevation has also been occasionally reported following nonsteroidal anti-inflammatory drugs (including aspirin), St. John's wort and kava.[19] Elevated levels of GGT can also be due to congestive heart failure.[20]

Individual test results should always be interpreted using the reference range from the laboratory that performed the test, though example reference ranges are 15-85 IU/L for men, and 5-55 IU/L for women.[21]

Examples[edit]

Human proteins that belong to this family include GGT1, GGT2, GGT6, GGTL3, GGTL4, GGTLA1 and GGTLA4.

References[edit]

  1. ^ Tate SS, Meister A (1985). "γ-glutamyl transpeptidase from kidney". Methods in Enzymology. 113: 400–419. doi:10.1016/S0076-6879(85)13053-3. ISBN 978-0-12-182013-8. PMID 2868390. 
  2. ^ Courtay C, Oster T, Michelet F, Visvikis A, Diederich M, Wellman M, Siest G (June 1992). "γ-glutamyltransferase: nucleotide sequence of the human pancreatic cDNA. Evidence for a ubiquitous γ-glutamyltransferase polypeptide in human tissues". Biochemical Pharmacology. 43 (12): 2527–2533. doi:10.1016/0006-2952(92)90140-E. PMID 1378736. 
  3. ^ Dominici S, Paolicchi A, Corti A, Maellaro E, Pompella A (2005). "Prooxidant reactions promoted by soluble and cell-bound γ-glutamyltransferase activity". Meth. Enzymol. 401: 483–500. doi:10.1016/S0076-6879(05)01029-3. PMID 16399404. 
  4. ^ 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. 
  5. ^ Meister A (August 1974). "The gamma-glutamyl cycle. Diseases associated with specific enzyme deficiencies". Ann. Intern. Med. 81 (2): 247–53. doi:10.7326/0003-4819-81-2-247. PMID 4152527. 
  6. ^ 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 1453575free to read. PMID 2860060. 
  7. ^ 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. 
  8. ^ Yokoyama H (June 2007). "[Gamma glutamyl transpeptidase (gammaGTP) in the era of metabolic syndrome]". Nihon Arukoru Yakubutsu Igakkai Zasshi (in Japanese). 42 (3): 110–24. PMID 17665541. 
  9. ^ 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. 
  10. ^ 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. 
  11. ^ Emdin M, Pompella A, Paolicchi A (2005). "Editorial - Gamma-glutamyltransferase, atherosclerosis, and cardiovascular disease: triggering oxidative stress within the plaque". Circulation. 112 (14): 2078–80. doi:10.1161/CIRCULATIONAHA.105.571919. PMID 16203922. 
  12. ^ Pompella A, Emdin M, Passino C, Paolicchi A (2004). "The significance of serum gamma-glutamyltransferase in cardiovascular diseases". Clin. Chem. Lab. Med. 42 (10): 1085–91. doi:10.1515/CCLM.2004.224. PMID 15552264. 
  13. ^ a b Franzini M, Bramanti E, Ottaviano V, Ghiri E, Scatena F, Pompella A, Donato L, Emdin M, Paolicchi A (2006). "A high performance gel filtration chromatography method for gamma-glutamyltransferase fraction analysis". Anal. Biochem. 374: 1–8. doi:10.1016/j.ab.2007.10.025. PMID 18023410. 
  14. ^ Lim JS, Lee DH, Park JY, Jin SH, Jacobs DR (Jun 2007). "A strong interaction between serum gamma-glutamyltransferase and obesity on the risk of prevalent type 2 diabetes: results from the Third National Health and Nutrition Examination Survey". Clinical Chemistry. 53 (6): 1092–1098. doi:10.1373/clinchem.2006.079814. PMID 17478563. 
  15. ^ 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. doi:10.1016/0009-8981(74)90225-3. 
  16. ^ Kaplan MM, et al. (1985). "Biochemical basis for serum enzyme abnormalities in alcoholic liver disease". In Chang NC, Chan NM. Early identification of alcohol abuse. Research Monograph No. 17. NIAAA. p. 186. 
  17. ^ Barouki R, Chobert MN, Finidori J, Aggerbeck M, Nalpas B, Hanoune J (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. 
  18. ^ Rosalki SB, Tarlow D, Rau D (August 1971). "Plasma gamma-glutamyl transpeptidase elevation in patients receiving enzyme-inducing drugs". Lancet. 2 (7720): 376–7. doi:10.1016/S0140-6736(71)90093-6. PMID 4105075. 
  19. ^ "Kava Uses, Benefits & Dosage". Herbal Database. Drugs.com. 
  20. ^ Ruttmann E, Brant LJ, Concin H, Diem G, Rapp K, Ulmer H (October 2005). "Gamma-glutamyltransferase as a risk factor for cardiovascular disease mortality: an epidemiological investigation in a cohort of 163,944 Austrian adults". Circulation. 112 (14): 2130–7. doi:10.1161/CIRCULATIONAHA.105.552547. PMID 16186419. 
  21. ^ General Laboratory Manual (PDF). Department of Pathology, Hackensack University Medical Centre. 2012. p. 129. Retrieved 20 February 2014. 

External links[edit]

GGTP is raised with raised Serum ferritin, cause not clearly known.