Figure 1.

The Vitamin K cycle. Glu-residues are gamma-carboxylated by GGCX to Gla-residues, an enzymatic process using VKH₂, O₂ and CO₂ as cofactors. During this process, VKH₂ is oxidized to VK epoxide, which is then reduced to VK and in a second reduction step to VKH₂ by VKORC1. Then, VKH₂ can be reused, the reason for which this process is called the VK cycle. Gamma-carboxylation is only performed in VKDP and is essential for their activation and downstream functioning in multiple biological processes, such as blood clotting, bone formation, inflammation and cell proliferation. Warfarin inhibits the VK cycle by preventing VK reduction. C: carbon; GGCX: gamma-glutamyl carboxylase; Gla: gamma-carboxyglutamate; Glu: glutamate; H: hydrogen; O: oxygen; R: attached hydrogen or a hydrocarbon side chain of any length; VK: vitamin K (quinone); VKDP: VK-dependent proteins; VKH₂: vitamin K hydroquinone; VKORC1: vitamin K epoxide reductase complex, subunit 1.