Blood：华法林对维生素K代谢的影响

2018-04-02 MedSci MedSci原创

抗凝剂华法林可抑制维生素K氧化还原酶（VKORC1）的活性，VKORC1可催化合成参与维生素K依赖性（VKD）蛋白质的羧基化过程和激活。VKORC1通过两个反应催化产生KH2：将维生素K环氧化物（KO）还原成醌（K），再进一步还原成KH2；而研究人员将整体的还原反应与分解的单个反应相对比发现了一种令人惊讶的华法林抑制机制。研究人员在野生型CKORC1或导致华法林耐药的突变体（Y139H、Y139F

抗凝剂华法林可抑制维生素K氧化还原酶（VKORC1）的活性，VKORC1可催化合成参与维生素K依赖性（VKD）蛋白质的羧基化过程和激活。

VKORC1通过两个反应催化产生KH2：将维生素K环氧化物（KO）还原成醌（K），再进一步还原成KH2；而研究人员将整体的还原反应与分解的单个反应相对比发现了一种令人惊讶的华法林抑制机制。

研究人员在野生型CKORC1或导致华法林耐药的突变体（Y139H、Y139F）中，比较华法林对KO还原至K的抑制作用和华法林对需要完整的还原反应的羧基化过程的抑制作用，结果发现，对羧基化作用的抑制，比对KO还原反应的抑制更强烈（400倍作用 vs 2-3倍）。

此外，研究人员利用抑制KO-K的还原反应降低K的水平来分析K-KH2的反应。仅需要K-KH2还原反应的羧基化作用被抑制的程度远低于需要全部还原VKORC1的KO底物所受到的抑制（在表达野生型VKORC1和细胞因子IX的细胞中，分别大约为2.5倍 vs 70倍）。

该结果表明华法林将彻底还原KO的两个反应解偶联。华法林耐受性醌还原酶次要活性的缺失提示解偶联。但是，293T细胞表达的IX因子和该还原酶活性对羧基化作用的抑制作用相对弱很多。

总而言之，该活性似乎与VKORC1协同催化整个KO还原反应。由于VKD蛋白在多种组织的多种生理过程中发挥作用，因此华法林治疗期间的如果发生协同作用可导致重大后果，但如果次要活性不像VKORC1一样广泛表达，可能会导致羧基化效率低下、功能异常。

原始出处：

Mark A.Rishavy，et al.Warfarin alters vitamin K metabolism： a surprising mechanism of VKORC1 uncoupling necessitates an additional reductase.Blood 2018 ：blood-2017-09-804666； doi： https：//doi.org/10.1182/blood-2017-09-804666

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2018-04-04 bsmagic9133

#维生素K#

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2018-04-03 flysky120

学习维生素K的作用.谢谢

73 0
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2018-04-03 1dd8c52fm63(暂无匿称)

学习学习.了解了解

65 0
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2018-04-03 121832a9m88暂无昵称

学习了

66 0
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2018-04-03 1209e435m98(暂无昵称)

学习了.谢谢分享

0 0
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2018-04-03 飛歌

学习了很有用不错

59 0
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2018-04-02 清风拂面

谢谢分享学习

22 0
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2018-04-02 1e1b8538m79(暂无匿称)

不错的文章值得拥有

29 0
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2018-04-02 惠映实验室

学习了.谢谢分享.

15 0
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2018-04-02 戒馋，懒，贪

谢谢分享学习了

15 0