Warfarin alters vitamin K metabolism: a surprising mechanism of VKORC1 uncoupling necessitates an additional reductase-Reference-Cited by-同舟云学术

Warfarin alters vitamin K metabolism: a surprising mechanism of VKORC1 uncoupling necessitates an additional reductase

Published:2018-06-21 Issue:25 Volume:131 Page:2826-2835
ISSN:0006-4971
Container-title:Blood
language:en
Short-container-title:

Author:

Rishavy Mark A.¹,Hallgren Kevin W.¹,Wilson Lee¹,Singh Savita¹,Runge Kurt W.²^ORCID,Berkner Kathleen L.¹^ORCID

Affiliation:

1. Department of Molecular Cardiology and

2. Department of Immunology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH

Abstract

Key Points Analysis of full VKORC1 reduction of vitamin K epoxide vs the individual reactions shows that warfarin uncouples the 2 reactions. A mutant becomes more active than wild-type VKORC1 only in the presence of warfarin, revealing a novel mechanism for warfarin resistance.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

Link

http://ashpublications.org/blood/article-pdf/131/25/2826/1466395/blood804666.pdf

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4. VKORC1 deficiency in mice causes early postnatal lethality due to severe bleeding;Spohn;Thromb Haemost,2009

5. Fatal hemorrhage in mice lacking gamma-glutamyl carboxylase;Zhu;Blood,2007

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