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Establishment of the Variation of Vitamin K Status According to Vkorc1 Point Mutations Using Rat Models

Vitamin K is crucial for many physiological processes such as coagulation, energy metabolism, and arterial calcification prevention due to its involvement in the activation of several vitamin K-dependent proteins. During this activation, vitamin K is converted into vitamin K epoxide, which must be r...

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Autores principales: Debaux, Jean Valéry, Hammed, Abdessalem, Barbier, Brigitte, Chetot, Thomas, Benoit, Etienne, Lefebvre, Sébastien, Lattard, Virginie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770205/
https://www.ncbi.nlm.nih.gov/pubmed/31484376
http://dx.doi.org/10.3390/nu11092076
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author Debaux, Jean Valéry
Hammed, Abdessalem
Barbier, Brigitte
Chetot, Thomas
Benoit, Etienne
Lefebvre, Sébastien
Lattard, Virginie
author_facet Debaux, Jean Valéry
Hammed, Abdessalem
Barbier, Brigitte
Chetot, Thomas
Benoit, Etienne
Lefebvre, Sébastien
Lattard, Virginie
author_sort Debaux, Jean Valéry
collection PubMed
description Vitamin K is crucial for many physiological processes such as coagulation, energy metabolism, and arterial calcification prevention due to its involvement in the activation of several vitamin K-dependent proteins. During this activation, vitamin K is converted into vitamin K epoxide, which must be re-reduced by the VKORC1 enzyme. Various VKORC1 mutations have been described in humans. While these mutations have been widely associated with anticoagulant resistance, their association with a modification of vitamin K status due to a modification of the enzyme efficiency has never been considered. Using animal models with different Vkorc1 mutations receiving a standard diet or a menadione-deficient diet, we investigated this association by measuring different markers of the vitamin K status. Each mutation dramatically affected vitamin K recycling efficiency. This decrease in recycling was associated with a significant alteration of the vitamin K status, even when animals were fed a menadione-enriched diet suggesting a loss of vitamin K from the cycle due to the presence of the Vkorc1 mutation. This change in vitamin K status resulted in clinical modifications in mutated rats only when animals receive a limited vitamin K intake totally consistent with the capacity of each strain to recycle vitamin K.
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spelling pubmed-67702052019-10-30 Establishment of the Variation of Vitamin K Status According to Vkorc1 Point Mutations Using Rat Models Debaux, Jean Valéry Hammed, Abdessalem Barbier, Brigitte Chetot, Thomas Benoit, Etienne Lefebvre, Sébastien Lattard, Virginie Nutrients Article Vitamin K is crucial for many physiological processes such as coagulation, energy metabolism, and arterial calcification prevention due to its involvement in the activation of several vitamin K-dependent proteins. During this activation, vitamin K is converted into vitamin K epoxide, which must be re-reduced by the VKORC1 enzyme. Various VKORC1 mutations have been described in humans. While these mutations have been widely associated with anticoagulant resistance, their association with a modification of vitamin K status due to a modification of the enzyme efficiency has never been considered. Using animal models with different Vkorc1 mutations receiving a standard diet or a menadione-deficient diet, we investigated this association by measuring different markers of the vitamin K status. Each mutation dramatically affected vitamin K recycling efficiency. This decrease in recycling was associated with a significant alteration of the vitamin K status, even when animals were fed a menadione-enriched diet suggesting a loss of vitamin K from the cycle due to the presence of the Vkorc1 mutation. This change in vitamin K status resulted in clinical modifications in mutated rats only when animals receive a limited vitamin K intake totally consistent with the capacity of each strain to recycle vitamin K. MDPI 2019-09-03 /pmc/articles/PMC6770205/ /pubmed/31484376 http://dx.doi.org/10.3390/nu11092076 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Debaux, Jean Valéry
Hammed, Abdessalem
Barbier, Brigitte
Chetot, Thomas
Benoit, Etienne
Lefebvre, Sébastien
Lattard, Virginie
Establishment of the Variation of Vitamin K Status According to Vkorc1 Point Mutations Using Rat Models
title Establishment of the Variation of Vitamin K Status According to Vkorc1 Point Mutations Using Rat Models
title_full Establishment of the Variation of Vitamin K Status According to Vkorc1 Point Mutations Using Rat Models
title_fullStr Establishment of the Variation of Vitamin K Status According to Vkorc1 Point Mutations Using Rat Models
title_full_unstemmed Establishment of the Variation of Vitamin K Status According to Vkorc1 Point Mutations Using Rat Models
title_short Establishment of the Variation of Vitamin K Status According to Vkorc1 Point Mutations Using Rat Models
title_sort establishment of the variation of vitamin k status according to vkorc1 point mutations using rat models
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770205/
https://www.ncbi.nlm.nih.gov/pubmed/31484376
http://dx.doi.org/10.3390/nu11092076
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