Просмотр кода страницы Английская Википедия:Gamma-glutamyltransferase

{{Английская Википедия/Панель перехода}}
{{Short description|Class of enzymes}}
{{cs1 config|name-list-style=vanc}}
{{Pfam_box 
| Symbol = G_glu_transpept 
| Name = Gamma-glutamyl transpeptidase 
| image = 
| width = 
| caption = 
| Pfam= PF01019
| InterPro= IPR000101
| SMART= 
| Prosite = PDOC00404
| SCOP =     
| TCDB = 
| OPM family= 
| OPM protein= 
| PDB= 
| Membranome superfamily = 274
}} 
{{Infobox enzyme
| Name       = gamma-glutamyltransferase
| EC_number  = 2.3.2.2
| CAS_number = 9046-27-9
| GO_code    = 0003840
| image      = GGT_structure.png
| width      =
| caption    = 
| name       = Gamma-glutamyltransferase 
}}
{{Infobox protein
| Name = [[GGT1|gamma-glutamyltransferase 1]]
| caption = 
| image = 
| width = 
| HGNCid = 4250
| Symbol = [[GGT1]]
| AltSymbols = GGT
| EntrezGene = 2678
| OMIM = 231950
| RefSeq = NM_001032364
| UniProt = P19440
| PDB = 
| ECnumber = 2.3.2.2
| Chromosome = 22
| Arm = q
| Band = 11.1-11.2
| LocusSupplementaryData = 
}}
{{Infobox protein
| Name = gamma-glutamyltransferase 2
| caption = 
| image = 
| width = 
| HGNCid = 4251
| Symbol = GGT2
| AltSymbols = GGT
| EntrezGene = 2679
| OMIM = 137181
| RefSeq = NM_002058
| UniProt = P36268
| PDB = 
| ECnumber = 2.3.2.2
| Chromosome = 22
| Arm = q
| Band = 11.1-11.2
| LocusSupplementaryData = 
}}

'''Gamma-glutamyltransferase''' (also '''γ-glutamyltransferase''', '''GGT''', '''gamma-GT''', '''gamma-glutamyl transpeptidase''';<ref name="Tate_1985"/> {{EC number|2.3.2.2}}) is a [[transferase]] (a type of [[enzyme]]) that [[catalysis|catalyzes]] the transfer of gamma-[[glutamic acid|glutamyl]] [[functional group]]s from molecules such as [[glutathione]] to an acceptor that may be an [[amino acid]], a [[peptide]] or water (forming [[glutamate]]).<ref name="Tate_1985"/><ref name = "Whitfield_2001"/>{{rp|268}} GGT plays a key role in the [[gamma-glutamyl cycle]], a pathway for the synthesis and degradation of glutathione as well as drug and [[xenobiotic]] detoxification.<ref name="Courtay_1992"/> Other lines of evidence indicate that GGT can also exert a [[pro-oxidant]] role, with regulatory effects at various levels in cellular [[signal transduction]] and cellular pathophysiology.<ref name =  "Dominici_2005" /> This transferase is found in many tissues, the most notable one being the [[liver]], and has significance in medicine as a diagnostic marker.

== Nomenclature ==
The name γ-glutamyltransferase is preferred by the Nomenclature Committee of the [[International Union of Biochemistry and Molecular Biology]].<ref name = "IUBMB" /><ref name="Whitfield_2001"/> The Expert Panel on Enzymes of the International Federation of Clinical Chemistry also used this name.<ref name = "Shaw_1983"/><ref name="Whitfield_2001"/> The older name is gamma-glutamyl transpeptidase  (GGTP).<ref name="Whitfield_2001"/>

== Function ==
GGT is present in the [[cell membrane]]s of many tissues, including the [[kidney]]s, [[bile duct]], [[pancreas]], [[gallbladder]], [[spleen]], [[heart]], [[brain]], and [[seminal vesicles]].<ref name = "Goldberg_1980" /> It is involved in the transfer of [[amino acid]]s across the [[cellular membrane]]<ref name = "Meister_1974" /> and [[leukotriene]] metabolism.<ref name = "Raulf_1985" /> It is also involved in glutathione [[metabolism]] by transferring the glutamyl [[Moiety (chemistry)|moiety]] to a variety of acceptor molecules including water, certain [[Levorotation|L]]-amino acids, and peptides, leaving the [[cysteine]] product to preserve [[intracellular]] [[homeostasis]] of [[oxidative stress]].<ref name = "Schulman_1975" /><ref name = "Yokoyama_2007" /> This general reaction is:

:(5-L-glutamyl)-peptide + an amino acid {{eqm}} peptide + 5-L-glutamyl amino acid

== Biochemistry ==
In prokaryotes and eukaryotes, GGT consists of two polypeptide chains, a heavy and a light subunit, processed from a single chain precursor by an autocatalytic cleavage.<ref name=":0">{{cite journal|last1=West|first1=Matthew B.|last2=Wickham|first2=Stephanie|last3=Quinalty|first3=Leslie M.|last4=Pavlovicz|first4=Ryan E.|last5=Li|first5=Chenglong|last6=Hanigan|first6=Marie H.|date=2011-08-19|title=Autocatalytic cleavage of human gamma-glutamyl transpeptidase is highly dependent on N-glycosylation at asparagine 95|journal=The Journal of Biological Chemistry|volume=286|issue=33|pages=28876–28888|doi=10.1074/jbc.M111.248823|issn=1083-351X|pmc=3190695|pmid=21712391|doi-access=free}}</ref> The active site of GGT is known to be located in the light subunit.{{Citation needed|date=December 2022}}

Co-translational [[N-glycosylation|''N''-glycosylation]] serves a significant role in the proper autocatalytic cleavage and proper folding of GGT. Single site mutations at asparagine residues were shown to result in a functionally active yet slightly less thermally stable version of the enzyme in vitro, while knockout of all asparagine residues resulted in an accumulation of the uncleaved, propeptide form of the enzyme.<ref name=":0" />

== Clinical significance ==
{{Anchor|GGT test}}
{{Redirect|GGT test|the test known as GTT|Glucose tolerance test}}
GGT is predominantly used as a diagnostic marker for [[liver disease]].{{Citation needed|date=December 2022}} Elevated [[Serum (blood)|serum]] GGT activity can be found in diseases of the liver, biliary system, pancreas and kidneys.<ref>{{cite journal |last1=Fine |first1=A. |last2=McIntosh |first2=W. B. |date=May 1975 |title=Elevation of Serum Gamma-Glutamyl Transpeptidase in End-Stage Chronic Renal Failure |url=http://journals.sagepub.com/doi/10.1177/003693307502000309 |journal=Scottish Medical Journal |language=en |volume=20 |issue=3 |pages=113–115 |doi=10.1177/003693307502000309 |issn=0036-9330 |pmid=242073 |s2cid=23177210}}</ref><ref>{{cite journal |last1=Endre |first1=Zoltán H. |last2=Pickering |first2=John W. |last3=Walker |first3=Robert J. |last4=Devarajan |first4=Prasad |last5=Edelstein |first5=Charles L. |last6=Bonventre |first6=Joseph V. |last7=Frampton |first7=Christopher M. |last8=Bennett |first8=Michael R. |last9=Ma |first9=Qing |last10=Sabbisetti |first10=Venkata S. |last11=Vaidya |first11=Vishal S. |last12=Walcher |first12=Angela M. |last13=Shaw |first13=Geoffrey M. |last14=Henderson |first14=Seton J. |last15=Nejat |first15=Maryam |date=2011-05-02 |title=Improved performance of urinary biomarkers of acute kidney injury in the critically ill by stratification for injury duration and baseline renal function |url= |journal=Kidney International |language=en |volume=79 |issue=10 |pages=1119–1130 |doi=10.1038/ki.2010.555 |issn=0085-2538 |pmc=3884688 |pmid=21307838 |last16=Schollum |first16=John B.W. |last17=George |first17=Peter M.}}</ref> Latent elevations in GGT are typically seen in patients with chronic [[viral hepatitis]] infections often taking 12 months or more to present.{{Citation needed|date=December 2022}}

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&nbsp;IU/L for men, and 5–55&nbsp;IU/L for women.<ref name="Mannion_2012" /> GGT is similar to [[alkaline phosphatase]] (ALP) in detecting disease of the [[biliary tract]]. Indeed, the two markers correlate well, though there are conflicting data about whether GGT has better [[Sensitivity and specificity|sensitivity]].<ref name="Betro_1973" /><ref name="Lum_1972" /> In general, ALP is still the first test for [[biliary disease]]. The main value of GGT over ALP is in verifying that GGT elevations are, in fact, due to biliary disease; ALP can also be increased in certain bone diseases, but GGT is not.<ref name="Lum_1972" />

=== Alcohol use ===
GGT is elevated by ingestion of large quantities of [[Ethanol|alcohol]]. However, determination of high levels of total serum GGT activity is  not specific to alcohol intoxication,<ref name = "Lamy_1974" /> and the measurement of selected serum forms of the enzyme offer more specific information.<ref name = "Franzini_2006" /> Isolated elevation or disproportionate elevation compared to other liver enzymes (such as ALT or [[alanine transaminase]]) can indicate harmful alcohol use or [[alcoholic liver disease]],<ref name = "Kaplan_1985" /> and can indicate excess alcohol consumption up to 3 or 4 weeks prior to the test.{{citation needed|date=February 2024}}  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 [[hepatocyte]]s.<ref name=  "Barouki _1983" />

=== Xenobiotics ===
Numerous drugs can raise GGT levels, including [[barbiturate]]s and [[phenytoin]].<ref name= "Rosalki_1971" /> GGT elevation has also been occasionally reported following [[nonsteroidal anti-inflammatory drug]]s (including [[aspirin]]), [[St. John's wort]] and [[kava]].<ref name="Drugs.com" />

=== Cardiovascular disease ===
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]],<ref name="Emdin_2006" /> suggesting a potential role in pathogenesis of cardiovascular diseases,<ref name="Pompella_2004" /> and circulates in blood in the form of distinct protein aggregates,<ref name="Franzini_2006" />  some of which appear to be related to specific pathologies such as [[metabolic syndrome]], [[alcohol addiction]] and [[chronic liver disease]].

Elevated levels of GGT can also be due to [[congestive heart failure]].<ref name="Ruttmann_2005" />

=== Neoplasms ===
GGT is expressed in high levels in many different tumors. It is known to accelerate tumor growth and to increase resistance to cisplatin in tumors.<ref>{{cite journal|last1=Hanigan|first1=M. H.|last2=Gallagher|first2=B. C.|last3=Townsend|first3=D. M.|last4=Gabarra|first4=V.|date=April 1999|title=Gamma-glutamyl transpeptidase accelerates tumor growth and increases the resistance of tumors to cisplatin in vivo|journal=Carcinogenesis|volume=20|issue=4|pages=553–559|doi=10.1093/carcin/20.4.553|issn=0143-3334|pmc=6522259|pmid=10223181}}</ref>

== Examples ==
Human proteins that belong to this family include [[GGT1]], [[GGT2]], [[GGT6 (gene)|GGT6]], [[GGTL3]], [[GGTL4]], [[GGTLA1]] and [[GGTLA4]].

== References ==
{{reflist | 33em | refs =

<ref name = "Drugs.com" >{{cite web | url = https://www.drugs.com/npp/kava.html | title = Kava Uses, Benefits & Dosage | publisher = Drugs.com | work = Herbal Database }}</ref>

<ref name = "IUBMB">{{cite web | url = http://www.chem.qmul.ac.uk/iubmb/enzyme/EC2/3/2/2.html |title=EC 2.3.2.2 | date = 2011 | publisher = International Union of Biochemistry and Molecular Biology | access-date = 9 October 2016 }}</ref>

<ref name = "Barouki _1983">{{cite journal | vauthors = Barouki R, Chobert MN, Finidori J, Aggerbeck M, Nalpas B, Hanoune J | title = Ethanol effects in a rat hepatoma cell line: induction of gamma-glutamyltransferase | journal = Hepatology | volume = 3 | issue = 3 | pages = 323–9 | year = 1983 | pmid = 6132864 | doi = 10.1002/hep.1840030308 | s2cid = 84080031 | doi-access = free }}</ref>

<ref name = "Betro_1973" >{{cite journal | vauthors = Betro MG, Oon RC, Edwards JB | title = Gamma-glutamyl transpeptidase in diseases of the liver and bone | journal = American Journal of Clinical Pathology | volume = 60 | issue = 5 | pages = 672–8 | date = November 1973 | pmid = 4148049 | doi =  10.1093/ajcp/60.5.672}}</ref>

<ref name = "Courtay_1992">{{cite journal | vauthors = Courtay C, Oster T, Michelet F, Visvikis A, Diederich M, Wellman M, Siest G | title = Gamma-glutamyltransferase: nucleotide sequence of the human pancreatic cDNA. Evidence for a ubiquitous gamma-glutamyltransferase polypeptide in human tissues | journal = Biochemical Pharmacology | volume = 43 | issue = 12 | pages = 2527–33 | date = June 1992 | pmid = 1378736 | doi = 10.1016/0006-2952(92)90140-E }}</ref>

<ref name = "Dominici_2005">{{cite book | vauthors = Dominici S, Paolicchi A, Corti A, Maellaro E, Pompella A | title = Prooxidant reactions promoted by soluble and cell-bound gamma-glutamyltransferase activity | chapter = Prooxidant Reactions Promoted by Soluble and Cell-Bound γ-Glutamyltransferase Activity | series = Methods in Enzymology | volume = 401 | pages = [https://archive.org/details/gluthionetransfe00sies/page/484 484–501] | year = 2005 | pmid = 16399404 | doi = 10.1016/S0076-6879(05)01029-3 | isbn = 9780121828066 | chapter-url = https://archive.org/details/gluthionetransfe00sies/page/484 }}</ref>

<ref name = "Emdin_2006" >{{cite journal | vauthors = Emdin M, Pompella A, Paolicchi A | title = Gamma-glutamyltransferase, atherosclerosis, and cardiovascular disease: triggering oxidative stress within the plaque | journal = Circulation | volume = 112 | issue = 14 | pages = 2078–80 | date = October 2005 | pmid = 16203922 | doi = 10.1161/CIRCULATIONAHA.105.571919 | doi-access = free }}</ref>

<ref name = "Franzini_2006" >{{cite journal | vauthors = Franzini M, Bramanti E, Ottaviano V, Ghiri E, Scatena F, Barsacchi R, Pompella A, Donato L, Emdin M, Paolicchi A | title = A high performance gel filtration chromatography method for gamma-glutamyltransferase fraction analysis | journal = Analytical Biochemistry | volume = 374 | issue = 1 | pages = 1–6 | date = March 2008 | pmid = 18023410 | doi = 10.1016/j.ab.2007.10.025 | hdl = 11382/3163 | hdl-access = free }}</ref>

<ref name = "Goldberg_1980" >{{cite journal | vauthors = Goldberg DM | title = Structural, functional, and clinical aspects of gamma-glutamyltransferase | journal = CRC Critical Reviews in Clinical Laboratory Sciences | volume = 12 | issue = 1 | pages = 1–58 | year = 1980 | pmid = 6104563 | doi = 10.3109/10408368009108725 }}</ref>

<ref name = "Kaplan_1985">{{cite book| vauthors = Kaplan MM, Matloff DS, Selinger MJ, Quaroni EG|  chapter= Biochemical basis for serum enzyme abnormalities in alcoholic liver disease | title= Early identification of alcohol abuse, Proceedings of a workshop October 31–November 1, 1983| veditors = Chang NC, Chao HM | id= Research Monograph No. 17|location=Rockville, Maryland| publisher = National Institute on Alcohol Abuse and Alcoholism| year = 1985 | pages = 186-198|lccn=84601128}}</ref>

<ref name = "Lamy_1974" >{{cite journal | vauthors = Lamy J, Baglin MC, Ferrant JP, Weill J | title = Determination de la gamma-glutamyl transpeptidase senque des ethyliques a la suite du sevrage | journal = Clin Chim Acta | year = 1974 | volume = 56 | issue = 2 | pages = 169–73 | doi=10.1016/0009-8981(74)90225-3| pmid = 4154814 }}</ref>

<ref name = "Lum_1972">{{cite journal | vauthors = Lum G, Gambino SR | title = Serum gamma-glutamyl transpeptidase activity as an indicator of disease of liver, pancreas, or bone | journal = Clinical Chemistry | volume = 18 | issue = 4 | pages = 358–62 | date = April 1972 | doi = 10.1093/clinchem/18.4.358 | pmid = 5012259 | doi-access = free }}</ref>

<ref name = "Mannion_2012">{{cite book | first = Ciaran M. | last = Mannion | url = http://www.hackensackumc.org/assets/1/7/General_Laboratory_Manual.pdf | title = General Laboratory Manual |page=129 |publisher=Department of Pathology, Hackensack University Medical Centre |year=2012 |access-date=20 February 2014}}</ref>

<ref name = "Meister_1974">{{cite journal | vauthors = Meister A | title = The gamma-glutamyl cycle. Diseases associated with specific enzyme deficiencies | journal = Annals of Internal Medicine | volume = 81 | issue = 2 | pages = 247–53 | date = August 1974 | pmid = 4152527 | doi = 10.7326/0003-4819-81-2-247 }}</ref>

<ref name = "Pompella_2004" >{{cite journal | vauthors = Pompella A, Emdin M, Passino C, Paolicchi A | title = The significance of serum gamma-glutamyltransferase in cardiovascular diseases | journal = Clinical Chemistry and Laboratory Medicine | volume = 42 | issue = 10 | pages = 1085–91 | year = 2004 | pmid = 15552264 | doi = 10.1515/CCLM.2004.224 | s2cid = 4248204 }}</ref>

<ref name = "Raulf_1985">{{cite journal | vauthors = Raulf M, Stüning M, König W | title = Metabolism of leukotrienes by L-gamma-glutamyl-transpeptidase and dipeptidase from human polymorphonuclear granulocytes | journal = Immunology | volume = 55 | issue = 1 | pages = 135–47 | date = May 1985 | pmid = 2860060 | pmc = 1453575 }}</ref>

<ref name = "Rosalki_1971" >{{cite journal | vauthors = Rosalki SB, Tarlow D, Rau D | title = Plasma gamma-glutamyl transpeptidase elevation in patients receiving enzyme-inducing drugs | journal = Lancet | volume = 2 | issue = 7720 | pages = 376–7 | date = August 1971 | pmid = 4105075 | doi = 10.1016/S0140-6736(71)90093-6 }}</ref>

<ref name = "Ruttmann_2005">{{cite journal | vauthors = Ruttmann E, Brant LJ, Concin H, Diem G, Rapp K, Ulmer H | title = Gamma-glutamyltransferase as a risk factor for cardiovascular disease mortality: an epidemiological investigation in a cohort of 163,944 Austrian adults | journal = Circulation | volume = 112 | issue = 14 | pages = 2130–7 | date = October 2005 | pmid = 16186419 | doi = 10.1161/CIRCULATIONAHA.105.552547 | doi-access =  }}</ref>

<ref name = "Schulman_1975">{{cite journal | vauthors = Schulman JD, Goodman SI, Mace JW, Patrick AD, Tietze F, Butler EJ | title = Glutathionuria: inborn error of metabolism due to tissue deficiency of gamma-glutamyl transpeptidase | journal = Biochemical and Biophysical Research Communications | volume = 65 | issue = 1 | pages = 68–74 | date = July 1975 | pmid = 238530 | doi = 10.1016/S0006-291X(75)80062-3 }}</ref>

<ref name = "Shaw_1983">{{cite journal | vauthors = Shaw LM, Strømme JH, London JL, Theodorsen L | title = International Federation of Clinical Chemistry. Scientific Committee, Analytical Section. Expert Panel on Enzymes. IFCC methods for measurement of enzymes. Part 4. IFCC methods for gamma-glutamyltransferase [(gamma-glutamyl)-peptide: amino acid gamma-glutamyltransferase, EC 2.3.2.2]. IFCC Document, Stage 2, Draft 2, 1983-01 with a view to an IFCC Recommendation | journal = Clinica Chimica Acta; International Journal of Clinical Chemistry | volume = 135 | issue = 3 | pages = 315F–338F | date = December 1983 | pmid = 6141014 | doi = 10.1016/0009-8981(83)90291-7 }}</ref>

<ref name = "Tate_1985">{{cite book | vauthors = Tate SS, Meister A | title = gamma-Glutamyl transpeptidase from kidney | chapter = &#91;50&#93; γ-Glutamyl transpeptidase from kidney | series = Methods in Enzymology | volume = 113 | pages = [https://archive.org/details/glutamateglutami0000unse/page/400 400–19] | year = 1985 | pmid = 2868390 | doi = 10.1016/S0076-6879(85)13053-3 | isbn = 978-0-12-182013-8 | chapter-url = https://archive.org/details/glutamateglutami0000unse/page/400 }}</ref>

<ref name = "Whitfield_2001">{{cite journal | vauthors = Whitfield JB | title = Gamma glutamyl transferase | journal = Critical Reviews in Clinical Laboratory Sciences | volume = 38 | issue = 4 | pages = 263–355 <!--| page = 268--> | date = August 2001 | pmid = 11563810 | doi = 10.1080/20014091084227 | s2cid = 1070555 }}</ref>

<ref name = "Yokoyama_2007">{{cite journal | vauthors = Yokoyama H | title = [Gamma glutamyl transpeptidase (gammaGTP) in the era of metabolic syndrome] | language = ja | journal = Nihon Arukōru Yakubutsu Igakkai Zasshi = Japanese Journal of Alcohol Studies & Drug Dependence | volume = 42 | issue = 3 | pages = 110–24 | date = June 2007 | pmid = 17665541 }}</ref>

}}

== External links ==
* {{MedlinePlusEncyclopedia|003458|Gamma-glutamyl transpeptidase (GGT) blood test}}
* {{MeshName|gamma-Glutamyltransferase}}
* [https://www.testing.com/tests/gamma-glutamyl-transferase-ggt/ GGT] - Lab Tests Online
* {{PDBe-KB2|P19440|Gamma-glutamyltransferase 1}}

{{Amino acid metabolism enzymes}}
{{Eicosanoid metabolism enzymes}}
{{Clinical biochemistry blood tests}}
{{Acyltransferases}}
{{Enzymes}}
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[[Category:Chemical pathology]]
[[Category:EC 2.3.2]]
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