Vitamin K-dependent gamma-glutamyl carboxylase (GGCX)

Vitamin K-dependent gamma-glutamyl carboxylase (GGCX) is an integral membrane enzyme located in the endoplasmic reticulum. It catalyzes the post-translational modification of specific glutamate (Glu) residues to gamma-carboxyglutamate (Gla) residues in vitamin K-dependent proteins. This modification is essential for the biological activity of several proteins, most notably those involved in blood coagulation, bone metabolism, and vascular health. The formation of Gla domains enables these proteins to bind calcium ions, which is critical for their function, especially for blood clotting factors such as prothrombin (F2), factor VII (F7), factor IX (F9), and factor X (F10). GGCX also modifies non-coagulation proteins like osteocalcin and matrix Gla protein. Warfarin acts indirectly on this pathway by inhibiting VKORC1—the enzyme responsible for recycling oxidized vitamin K—thus reducing substrate availability for gamma-glutamyl carboxylase.

Inhibition of VKORC1, reducing substrate availability for gamma-glutamyl carboxylase