Gamma-glutamyl transferase or gamma-glutamyl transpeptidase (also γ-glutamyl transferase, GGT, GGTP, gamma-GT) (EC18.104.22.168) 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 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. 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.
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.
GGT is predominantly used as a diagnostic marker for liver disease in medicine, 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. 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. 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, suggesting a potential role in pathogenesis of cardiovascular diseases, and circulates in blood in the form of distinct protein aggregates, 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.
GGT is elevated by large quantities of alcohol ingestion. However, determination of high levels of total serum GGT activity is not specific to alcohol intoxication, and the measurement of selected serum forms of the enzyme offer more specific information. Isolated elevation or disproportionate elevation compared to other liver enzymes (such as ALP or ALT) can indicate alcohol abuse or alcoholic liver disease. 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.
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.
^Courtay C, Oster T, Michelet F, Visvikis A, Diederich M, Wellman M et al. (Jun 1992). "Gamma-glutamyltransferase: nucleotide sequence of the human pancreatic cDNA. Evidence for a ubiquitous gamma-glutamyltransferase polypeptide in human tissues". Biochemical Pharmacology43 (12): 2527–2533. doi:10.1016/0006-2952(92)90140-E. PMID1378736.
^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. PMID16399404.
^Schulman J, Goodman S, Mace J, Patrick A, Tietze F, Butler E (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. PMID238530.
^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. PMID17665541.
^Betro M, Oon R, Edwards J (November 1973). "Gamma-glutamyl transpeptidase in diseases of the liver and bone". Am. J. Clin. Pathol.60 (5): 672–8. PMID4148049.
^ abLum G, Gambino S (April 1972). "Serum gamma-glutamyl transpeptidase activity as an indicator of disease of liver, pancreas, or bone". Clin. Chem.18 (4): 358–62. PMID5012259.
^Emdin M, Pompella A, Paolicchi A (2005). "Editorial - Gamma-glutamyltransferase, atherosclerosis, and cardiovascular disease: triggering oxidative stress within the plaque". Circulation112 (14): 2078–80. doi:10.1161/CIRCULATIONAHA.105.571919. PMID16203922.
^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. PMID15552264.
^ abFranzini M, Bramanti E, Ottaviano V, Ghiri E, Scatena F, Pompella A et al. (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. PMID18023410.
^Lamy J, Baglin M, Ferrant J, Weill J (1974). "Determination de la gamma-glutamyl transpeptidase senque des ethyliques a la suite du sevrage". Clin Chim Acta56: 169. doi:10.1016/0009-8981(74)90225-3.
^Kaplan MM, et al. (1985). Chang NC, Chan NM, ed. Biochemical basis for serum enzyme abnormalities in alcoholic liver disease. Research Monograph No. 17 (in Early identification of alcohol abuse) (NIAAA). p. 186.
^Barouki R, Chobert M, Finidori J, Aggerbeck M, Nalpas B, Hanoune J (1983). "Ethanol effects in a rat hepatoma cell line: induction of gamma-glutamyltransferase". Hepatology3 (3): 323–9. doi:10.1002/hep.1840030308. PMID6132864.
^Ruttmann E, Brant L, 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". Circulation112 (14): 2130–7. doi:10.1161/CIRCULATIONAHA.105.552547. PMID16186419.