Carboxyglutamic acid

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Gamma-carboxyglutamic acid
)
Carboxyglutamic acid
Names
Systematic IUPAC name
3-Aminopropane-1,1,3-tricarboxylic acid
Other names
γ-Carboxyglutamate
Identifiers
3D model (
JSmol
)
ChemSpider
ECHA InfoCard
 100.054.607 Edit this at Wikidata
UNII
  • 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
  • O=C(O)C(C(=O)O)CC(N)C(=O)O
Properties
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).

Carboxyglutamic acid (or the conjugate base, carboxyglutamate), is an uncommon

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 γ-carboxylation of clotting factors II, VII, IX, X and protein Z.[1]

Synthesis

In the biosynthesis of γ-carboxyglutamic acid, the γ-proton on glutamic acid is abstracted, and CO2 is subsequently added. The reaction intermediate is a γ-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 γ-carbon. Then CO2 is added to the γ-carbon to form γ-carboxyglutamic acid.[2]

γ-Carboxyglutamic acid-rich (GLA) domain

Main article: Gla domain

A number of γ-carboxyglutamate residues are present in the γ-carboxyglutamic acid-rich ("GLA") domain. This GLA domain is known to be found in over a dozen known proteins, including coagulation factors X, VII, IX, and XIV,

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 high-affinity binding of calcium ions (Ca2+) to Gla proteins, which is often necessary for their conformation, and always necessary for their function.[3]

Role in coagulation

γ-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.

citrate
ion, causes their dysfunction, and prevents blood from coagulating. Thus, citrate addition to blood is the most common method of storing it in a liquid state between harvest and transfusion.

See also

References

  1. PMID 332061
    .
  2. PMID 10068650
    .
  3. ^ "Gamma-carboxyglutamic acid-rich (GLA) domain (IPR000294) < InterPro < EMBL-EBI". www.ebi.ac.uk. Retrieved 2015-12-22.
  4. PMID 1730085
    .
  5. PMID 8882309
    .
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