Figure 2. The role of vitamin K in activation of gla-proteins.

Vitamin K serves as a co-factor of activation of blood coagulation factors and matrix gla-protein (MGP) by γ-glutamyl carboxylase encoded by the GGCX gene. The γ-glutamyl carboxylase activates coagulation factors (Glu→ Gla), the carboxylated forms are secreted into circulation from hepatocytes and are required for normal blood coagulation (lower panel). In peripheral connective tissue cells, such as fibroblasts, similar activation of uncarboxylated MGP (ucMGP) normally takes place resulting in carboxylated matrix gla-protein (cMGP) which is required for prevention of unwanted mineralization of peripheral tissues under normal calcium and phosphate homeostatic conditions (upper panel). It has been postulated that ABCC6 serves as a transporter molecule transporting vitamin K derivatives, such as the reduced form (KH₂) conjugated with glutathione (GSH). In the absence of ABCC6 transporter activity in PXE, the specific vitamin K co-factor concentrations in the serum and in fibroblasts are reduced resulting in deficient activation of MGP and allowing ectopic mineralization in the adjacent connective tissue to take place. (Modified from Li et al., 2009a, with permission).