What is Gamma carboxylation of glutamic acid?
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Gamma-carboxyglutamic acid is synthesized by the post-translational modification of glutamic acid residues. This reaction, catalyzed by a hepatic carboxylase, requires reduced vitamin K, oxygen, and carbon dioxide. The function of gamma-carboxyglutamic acid is uncertain.
What does Gamma carboxylation do?
γ-Carboxylation γ-Glutamyl carboxylase oxidizes vitamin K while simultaneously adding CO2 to protein-bound glutamic acid to form γ-carboxyglutamic acid (known as ‘Gla’), which allows these proteins to bind calcium (carboxylation). γ-Carboxylated proteins are involved in both bone formation and in blood coagulation.
What is the significance of gamma carboxylation in blood clotting?
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.
What is the role of vitamin K in gamma carboxylation?
Vitamin K is a cofactor for the enzymatic conversion of glutamic acid (Glu) residues to gamma-carboxyglutamic acid (Gla) in vitamin K-dependent proteins, via the endoplasmic reticulum resident vitamin K-dependent gamma-glutamyl carboxylase.
What are Gla residues?
The Gla domains contain 9–12 Glu residues that are γ-carboxylated in a post-translational process that require vitamin K. The γ-carboxylated Glu residues (Gla residues) mediate the binding of Ca2+ ions and are crucial for the membrane interaction.
What is the main role of gamma-carboxyglutamic acid residues in proteins?
The γ-carboxyglutamic acid residues and the bound calcium ions are solvent exposed. The calcium-carboxylate networks of the factor IX Gla-domain and conantokin G. One role of γ-carboxyglutamic acid is to stabilize a protein structure by formation of an extended calcium-carboxylate network.
Which factors are converted from Glu residues to Gla residues with the help of vitamin K oxidation and reduction?
Vitamin K cycle. During vitamin K-dependent carboxylation, glutamate (Glu) is converted to gamma-carboxyglutamte (Gla) by gamma-glutamyl carboxylase (GGCX) using a reduced form of vitamin K (KH2), carbon dioxide, and oxygen as cofactors. KH2 is oxidized to vitamin K epoxide (KO).
What is carboxylation in biology?
Carboxylation is a chemical reaction in which a carboxylic acid is produced by treating a substrate with carbon dioxide. The opposite reaction is decarboxylation.
What is the main role of gamma carboxyglutamic acid residues in proteins?
Why is carboxylation important?
It is essential for the biological function of proteins that control blood coagulation, vascular calcification, bone metabolism, and other important physiological processes. 1 Carboxylation has mostly been associated with coagulation, since it was originally observed in the clotting factor, prothrombin (PT).
What is GLA in biology?
Vitamin K-dependent carboxylation/gamma-carboxyglutamic (GLA) domain is a protein domain that contains post-translational modifications of many glutamate residues by vitamin K-dependent carboxylation to form γ-carboxyglutamate (Gla). Proteins with this domain are known informally as Gla proteins.
What amino acid residue is required for factor VII activation?
Factor VII is synthesized in the liver and vitamin K is vital for post-translational γ-carboxylation of glutamic acid residues in the molecule. Without these modifications the factor is unable to participate in calcium-dependent binding to phospholipid and has no coagulant activity.
What is gamma glutamyl carboxylase?
Gamma-Glutamyl Carboxylase. γ-Glutamyl carboxylase is an integral membrane glycoprotein that requires vitamin K to activate posttranslational modification of glutamate (Glu) to γ-carboxyl glutamate (Gla) in specific vitamin K-dependent proteins.
What does gamma carboxylase do to vitamin K?
Gamma-glutamyl carboxylase oxidizes Vitamin K hydroquinone to Vitamin K 2,3 epoxide, while simultaneously adding CO 2 to protein-bound glutamic acid (abbreviation = Glu) to form gamma-carboxyglutamic acid (also called gamma-carboxyglutamate, abbreviation = Gla).
What are the cofactors involved in gamma carboxylation?
An essential cofactor for gamma-carboxylation is vitamin K, which is generated by the intestinal flora. During the carboxylation reaction the reduced form of vitamin K (hydroquinone) is oxidised by gamma-glutamyl carboxylase to vitamin K epoxide, which is then restored to the hydroquinone form by vitamin K epoxide reductase (VKOR).
How does the gamma-glutamyl carboxylase gene affect warfarin pharmacodynamics?
The gamma-glutamyl carboxylase (GGCX) enzyme plays an essential role in biosynthesis of vitamin K–dependent clotting factors by carboxylating protein-bound glutamate residues. Thus the GGCX gene is a candidate for affecting warfarin pharmacodynamics. Rare GGCX mutations cause deficiencies in vitamin K–dependent clotting factors.