Gamma-glutamyl carboxylase


Gamma-glutamyl carboxylase is an enzyme that in humans is encoded by the GGCX gene, located on chromosome 2 at 2p12.

Function

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. Most gla domain-containing proteins depend on this carboxylation reaction for posttranslational modification. In humans, the gamma-glutamyl carboxylase enzyme is most highly expressed in the liver.

Catalytic reaction

Gamma-glutamyl carboxylase oxidizes Vitamin K hydroquinone to Vitamin K 2,3 epoxide, while simultaneously adding CO2 to protein-bound glutamic acid to form gamma-carboxyglutamic acid. 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.
a -α-L-glutamate + phylloquinol + + oxygen →
a 4-carboxy-L-glutamate + vitamin K 2,3-epoxide + +

Clinical significance

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