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a unit of magnetic field strength equal to one-hundred-thousandth of an oersted
the 3rd letter of the Greek alphabet
a herd of whales

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ガンマ(ギリシア語アルファベットの第3字Γ,γ;英語のG,gに相当)
(特に女性の)魅力的な脚,すんなりした脚

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/01/06 00:46:04」(JST)

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Carboxyglutamic acid (or the conjugate base, carboxyglutamate), is an uncommon amino acid introduced into proteins by a post-translational carboxylation of glutamic acid residues. This modification is found, for example, in clotting factors and other proteins of the coagulation cascade. This modification introduces an affinity for calcium ions. In the blood coagulation cascade, Vitamin K is required to introduce gamma-carboxylation of clotting factors II, VII, IX, X and protein Z.^[1]

Synthesis

In the biosynthesis of -carboxyglutamic acid, the -proton on glutamic acid is abstracted, and CO₂ is subsequently added. The reaction intermediate is a -glutamyl carbanion.

This reaction is catalyzed by a carboxylase that requires Vitamin K as its cofactor. It is not exactly known how Vitamin K participates, but it is hypothesized that a free cysteine residue in the carboxylase converts vitamin K into an active strong base that in turn abstracts a hydrogen from glutamic acid's -carbon. Then CO₂ is added to the -carbon to form -carboxyglutamic acid. ^[2]

Fig. 1.

Gamma-carboxyglutamic acid-rich (GLA) domain

A number of gamma-carboxyglutamate (Gla) residues are present in the Gamma-carboxyglutamic acid-rich (GLA) domain. This GLA domain is known to be found in several proteins, including coagulation factors X, VII, IX, and XIV, vitamin K-dependent protein S and Z, prothrombin, transthyretin, osteocalcin, matrix Gla protein (MGP), inter-alpha trypsin inhibitor heavy chain H2, and growth arrest-specific protein 6 (Gas6). The Gla domain is responsible for the high-affinity binding of calcium ions.^[3]

Role in Coagulation

Gamma-carboxyglutamic acid residues play an important role in coagulation. The high-affinity calcium binding sites in the GLA domain of factor IX, which is a serine protease of the coagulation system, were found to partially mediate the binding of factor IXa to platelets and in factor-X activation.^[4] In addition, upon mechanical injury to the blood vessel wall, a cell-associated tissue factor becomes exposed and initiates a series of enzymatic reactions localized on a membrane surface generally provided by cells and accumulating platelets. Gla residues partly govern the activation and binding of circulating blood-clotting enzymes and zymogens to this exposed cell membrane surface. Specifically, gla residues are needed in calcium binding and in exposing hydrophobic membrane binding regions to the cell bilayer. Lack of these gla residues results in impaired coagulation or even anticoagulation, which may lead to bleeding diathesis or thrombosis.^[5]

References

^ J Stenflo, and J W Suttie. "Vitamin K-Dependent Formation of γ-Carboxyglutamic Acid". Annual Review of Biochemistry 46: 157–172. doi:10.1146/annurev.bi.46.070177.001105.
^ Furie, Bruce; Bouchard, Beth A.; Furie, Barbara C. (1999-03-15). "Vitamin K-Dependent Biosynthesis of γ-Carboxyglutamic Acid". Blood 93 (6): 1798–1808. ISSN 0006-4971. PMID 10068650.
^ "Gamma-carboxyglutamic acid-rich (GLA) domain (IPR000294) < InterPro < EMBL-EBI". www.ebi.ac.uk. Retrieved 2015-12-22.
^ Rawala-Sheikh, R.; Ahmad, S. S.; Monroe, D. M.; Roberts, H. R.; Walsh, P. N. (1992-01-15). "Role of gamma-carboxyglutamic acid residues in the binding of factor IXa to platelets and in factor-X activation". Blood 79 (2): 398–405. ISSN 0006-4971. PMID 1730085.
^ Kalafatis, M.; Egan, J. O.; van't Veer, C.; Mann, K. G. (1996-01-01). "Regulation and regulatory role of gamma-carboxyglutamic acid containing clotting factors". Critical Reviews in Eukaryotic Gene Expression 6 (1): 87–101. ISSN 1045-4403. PMID 8882309.

UpToDate Contents

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3. ガンマヒドロキシブチレート（GHB）中毒 gamma hydroxybutyrate ghb intoxication
4. ガンマヒドロキシブチレート（GHB）への依存および離脱 gamma hydroxybutyrate ghb dependence and withdrawal
5. ビタミンＫとγカルボキシグルタミン酸の合成および機能 vitamin k and the synthesis and function of gamma carboxyglutamic acid

English Journal

Effect of Anticoagulation with Citrate versus Heparin on the Adsorption of Coagulation Factors to Blood Purification Resins with Different Charge.

Tripisciano C, Leistner A, Linsberger I, Leistner A, Falkenhagen D, Weber V.SourceCenter for Biomedical Technology, Danube University Krems , Dr.-Karl-Dorrek-Straße 30, 3500 Krems, Austria.
Biomacromolecules.Biomacromolecules.2012 Feb 13;13(2):484-8. Epub 2012 Jan 31.
In liver failure, hydrophobic toxins accumulate in the blood circulation. To support hepatic function, extracorporeal blood purification systems have been developed, in which both cationic and neutral adsorbents are used to remove albumin-bound metabolites from blood. An issue of these systems is th
PMID 22229537

Molecular differentiation between osteophytic and articular cartilage - clues for a transient and permanent chondrocyte phenotype.

Gelse K, Ekici AB, Cipa F, Swoboda B, Carl HD, Olk A, Hennig FF, Klinger P.SourceDepartment of Orthopaedic Trauma Surgery, University Hospital Erlangen, Germany.
Osteoarthritis and cartilage / OARS, Osteoarthritis Research Society.Osteoarthritis Cartilage.2012 Feb;20(2):162-71. Epub 2011 Dec 13.
OBJECTIVE: To identify the molecular differences between the transient and permanent chondrocyte phenotype in osteophytic and articular cartilage.METHODS: Total RNA was isolated from the cartilaginous layer of osteophytes and from intact articular cartilage from knee joints of 15 adult human donors
PMID 22209871

Japanese Journal

Regulation of Osteoblast and Odontoblast Differentiation by RUNX2

Journal of oral biosciences 52(1), 22-25, 2010-02-20
NAID 10027105218

Gamma-carboxyglutamate-containing proteins and the vitamin K-dependent carboxylase

Biochem J 266, 625-636, 1990
NAID 80005104796

Gamma-carboxyglutamate excretion and calcinosis in juvenile dermatomyositis

Arthritis Rheum 25, 1094-1100, 1982
NAID 30025724437

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★リンクテーブル★

リンク元	「γカルボキシグルタミン酸」「1-carboxyglutamic acid」「gamma-carboxyglutamic acid」
関連記事	「gamma」「carboxyglutamate」

「γカルボキシグルタミン酸」

Carboxyglutamic acid
Names
	IUPAC name 3-Aminopropane-1,1,3-tricarboxylic acid
	Other names γ-Carboxyglutamate
Identifiers
CAS Number	53445-96-8
ChemSpider	37241
Jmol interactive 3D	Image
PubChem	40772
	InChI InChI=1/C6H9NO6/c7-3(6(12)13)1-2(4(8)9)5(10)11/h2-3H,1,7H2,(H,8,9)(H,10,11)(H,12,13) Key: UHBYWPGGCSDKFX-UHFFFAOYAH ;
	SMILES O=C(O)C(C(=O)O)CC(N)C(=O)O ;
Properties
Chemical formula	C6H9NO6
Molar mass	191.14 g/mol
Density	1.649 g/mL
Boiling point	418 °C (784 °F; 691 K)
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
	Infobox references