Figure 2: Vitamin K cycle and warfarin metabolism. Inactive zymogens, among which are the VK-dependent coagulation factors II, VII, IX, and X, are activated by gamma-carboxylation by the gamma-glutamyl carboxylase (GGCX). The cofactor for this carboxylation step is VK, which is transformed into VK epoxide. This epoxide is then reduced by the VK-epoxide reductase of VKORC1 to quinone. Warfarin specifically blocks the initial reduction step, while CYP4F2 catalyzes the formation of hydroxyvitamin K out of quinone.