Gamma-glutamyl carboxylase

Gamma-glutamyl carboxylase is an enzyme that catalyzes the posttranslational modification of vitamin K-dependent proteins. Many of these vitamin K-dependent proteins are involved in coagulation so the function of the encoded enzyme is essential for hemostasis.^[2] Most gla domain-containing proteins depend on this carboxylation reaction for posttranslational modification.^[3] In humans, the gamma-glutamyl carboxylase enzyme is most highly expressed in the liver.

Gamma-glutamyl carboxylase oxidizes vitamin K hydroquinone to Vitamin K-2,3-epoxide, while simultaneously adding CO₂ to protein-bound glutamic acid (abbreviation = Glu) to form gamma-carboxyglutamic acid (also called gamma-carboxyglutamate, abbreviation = Gla). Presence of two carboxylate groups causes chelation of Ca²⁺, resulting in change in tertiary structure of protein and its activation. The carboxylation reaction will only proceed if the carboxylase enzyme is able to oxidize vitamin K hydroquinone to vitamin K epoxide at the same time; the carboxylation and epoxidation reactions are said to be coupled reactions.^[4][5]

No experimental structure is known for GGCX, limiting understanding of its reaction mechanism. Based on the fact that the two reactions are coupled, a computational study is able to propose how the reactants interact with each other to form the products.^[6] Lys228 has been shown to be the residue responsible for starting the reaction.^[7] How the enzyme holds the reactants in place to have them interact with each other remains poorly shown. 491-507 and 395-401 are probably responsible for propeptide and glutamate binding respectively.^[8]

Mutations in this gene are associated with vitamin K-dependent coagulation defect and PXE-like disorder with multiple coagulation factor deficiency.^[2][9]

• Carboxyglutamate