Target type: biologicalprocess
The gamma-carboxylation of peptidyl-glutamic acid; catalyzed by the vitamin K dependent gamma-glutamyl carboxylase. [RESID:AA0032]
Peptidyl-glutamic acid carboxylation is a post-translational modification that involves the addition of a carboxyl group (COO-) to the γ-carboxyl group of glutamate residues in specific proteins. This modification is essential for the function of a variety of proteins involved in blood coagulation, bone metabolism, and other biological processes.
The process of peptidyl-glutamic acid carboxylation is catalyzed by a specific enzyme called γ-glutamyl carboxylase (GGCX). GGCX requires the presence of vitamin K as a cofactor. Vitamin K is first reduced to its hydroquinone form by an enzyme called vitamin K epoxide reductase. The reduced form of vitamin K is then oxidized by GGCX, which generates a reactive carbonium ion intermediate. This intermediate then reacts with the γ-carboxyl group of a glutamate residue in the protein substrate, resulting in the formation of a γ-carboxyglutamate (Gla) residue.
The presence of Gla residues in proteins is essential for their function. For example, in the case of blood coagulation factors, the Gla residues are responsible for binding calcium ions. Calcium binding is essential for the proper assembly of the coagulation factors into complexes that ultimately lead to the formation of a blood clot.
The process of peptidyl-glutamic acid carboxylation is tightly regulated. The activity of GGCX is regulated by a number of factors, including the availability of vitamin K, the levels of calcium ions, and the presence of specific protein inhibitors.
Defects in the process of peptidyl-glutamic acid carboxylation can lead to a number of diseases. For example, vitamin K deficiency can result in bleeding disorders, while mutations in the GGCX gene can cause a variety of skeletal disorders.'
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| Protein | Definition | Taxonomy |
|---|---|---|
| Vitamin K epoxide reductase complex subunit 1 | [no definition available] | Bos taurus (cattle) |
| Vitamin K-dependent gamma-carboxylase | A vitamin K-dependent gamma-carboxylase that is encoded in the genome of human. [PRO:DNx, UniProtKB:P38435] | Homo sapiens (human) |
| Vitamin K-dependent gamma-carboxylase | A vitamin K-dependent gamma-carboxylase that is encoded in the genome of human. [PRO:DNx, UniProtKB:P38435] | Homo sapiens (human) |
| Vitamin K epoxide reductase complex subunit 1 | A vitamin K epoxide reductase complex subunit 1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9BQB6] | Homo sapiens (human) |
| Vitamin K epoxide reductase complex subunit 1-like protein 1 | A vitamin K epoxide reductase complex subunit 1-like protein 1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q8N0U8] | Homo sapiens (human) |
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| vitamin k1 oxide | vitamin K1 oxide: RN given refers to parent cpd; see also record for 2,3-epoxymenaquinone | ||
| menatetrenone | menaquinone-4 : A menaquinone whose side-chain contains 4 isoprene units in an all-trans-configuration. | menaquinone | anti-inflammatory agent; antioxidant; bone density conservation agent; human metabolite; neuroprotective agent |
| warfarin | 4-hydroxy-3-(3-oxo-1-phenylbutyl)-1-benzopyran-2-one : A member of the class of coumarins that is 4-hydroxycoumarin which is substituted at position 3 by a 1-phenyl-3-oxo-1-butyl group. warfarin : A racemate comprising equal amounts of (R)- and (S)-warfarin. Extensively used as both an anticoagulant drug and as a pesticide against rats and mice. Warfarin: An anticoagulant that acts by inhibiting the synthesis of vitamin K-dependent coagulation factors. Warfarin is indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, pulmonary embolism, and atrial fibrillation with embolization. It is also used as an adjunct in the prophylaxis of systemic embolism after myocardial infarction. Warfarin is also used as a rodenticide. | benzenes; hydroxycoumarin; methyl ketone |