Gamma-glutamyl carboxylase (GGCX) (GGCX)

Gamma-glutamyl carboxylase (GGCX) is an integral membrane enzyme located in the endoplasmic reticulum that plays a pivotal role in the post-translational modification of vitamin K-dependent proteins (UniProt: P38435). It catalyzes the conversion of specific glutamate residues into gamma-carboxyglutamate (Gla) residues, a reaction that requires the reduced form of vitamin K, carbon dioxide, and oxygen (PMID: 24089220). This modification is essential for the activation of proteins involved in blood coagulation, as well as extra-hepatic proteins like osteocalcin and matrix Gla protein (MGP). Osteocalcin is necessary for proper bone mineralization, while MGP acts as a critical inhibitor of vascular and soft tissue calcification (PMID: 30974836). Vitamin K2 (menaquinone) serves as a key cofactor for GGCX in these peripheral tissues, and its deficiency leads to the accumulation of undercarboxylated, inactive forms of these proteins. Consequently, impaired GGCX activity or insufficient vitamin K2 intake is associated with increased risks of osteoporosis and arterial calcification (StatPearls: NBK482262). While GGCX is not the direct target of traditional anticoagulants like warfarin, its activity is indirectly suppressed by these drugs through the inhibition of vitamin K recycling.

Other names

Vitamin K-dependent gamma-carboxylasePeptidyl-glutamate 4-carboxylaseGCVKGC

Acts as a catalyst for the vitamin K-dependent carboxylation of glutamate residues to gamma-carboxyglutamate (Gla), enabling calcium-binding capabilities in target proteins (UniProt: P38435).