Warfarin and the Vitamin K-Dependent γ-Carboxylation System

Insight into the molecular basis for genetic warfarin resistance has recently been accomplished by the identification of an 18-kDa protein of the endoplasmic reticulum that is targeted by the drug. When expressed in eukaryotic and insect cells, the protein reduces vitamin K1 2,3-epoxide in a warfarin-sensitive reaction. This finding strongly suggests that the protein is part of the vitamin K cycle, which is essential for the production of vitamin K-dependent proteins. Identification of the 18-kDa protein has aided the understanding of the vitamin K-dependent γ-carboxylation system at the molecular level.