The genetics of vitamin K antagonists.
The genetics of vitamin K antagonists.
复制标题
维生素 K 拮抗剂的遗传学。
DOI：
10.1038/sj.tpj.6500258
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Eby,CS
中科院分区：
文献类型：
--
作者：
Gage,BF;Eby,CS
Coumarins such as warfarin (Coumadint and others) are the most popular oral anticoagulant. They inhibit the action of vitamin K epoxide reductase, whose gene (VKOR) has been newly discovered by two independent teams. 1, 2 In the absence of coumarin, the vitamin K cycle regenerates reduced vitamin K1 from its epoxide (Figure 1). Reduced vitamin K is a cofactor for post-translational у-carboxylation of glutamic acid residues on several proteins, including coagulation factors II (prothrombin), VII, IX, and X. Although coumarins also inhibit the у-carboxylation of anticoagulant proteins C, S, and Z, inhibition of clotting factor activity is their main pharmacologic effect. у-Carboxylation allows for normal hemostasis by resulting in negatively charged у-carboxyglutamates on factors II, VII, IX, and X, which bind to calcium cations and then to platelet phospholipid membranes. у-Carboxylation is also required for the development of other tissues, and warfarin exposure in utero can cause mental retardation, nasal hypoplasia, and limb or digit abnormalities in the fetus.
