Vitamin K recycling and mechanism of vitamin K antagonist (VKA) anticoagulants

• Fully oxidized (2 disulfides): vitamin K epoxide
• Partially oxidized (1 disulfide): vitamin K quinone
• Reduced (no disulfides): vitamin K hydroquinone (KH2), the active cofactor for gamma-glutamyl carboxylase.

Gamma carboxylation causes oxidation of vitamin K, and the vitamin must be recycled to the active (reduced) form after every gamma carboxylation reaction.

• VKOR catalyzes sequential reduction of vitamin K.
• Vitamin K antagonists such as warfarin and brodifacoum (long-acting anticoagulant rodenticide) act by inhibiting VKOR and preventing vitamin K recycling, in turn making vitamin K unavailable for gamma carboxylating vitamin K-dependent clotting factors (II, VII, IX, and X).