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

• Published in: Nutrients Vol. 11; no. 9; p. 2076
• Main Authors: Debaux, Jean Valéry, Hammed, Abdessalem, Barbier, Brigitte, Chetot, Thomas, Benoit, Etienne, Lefebvre, Sébastien, Lattard, Virginie
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.09.2019; MDPI
• Subjects: Animal biology; Animal models; Animals; Anticoagulants; Biochemistry; Biochemistry, Molecular Biology; Calcification; Calcium; Calcium - metabolism; Clotting; Coagulation; Cytochrome P450; Cytochromes P450; Diet; Drug Administration Schedule; Ecotoxicology; Enzymes; Females; Food and Nutrition; Gene Expression Regulation, Enzymologic; Genotype; Life Sciences; Male; Males; Metabolism; Microsomes, Liver; Mutation; osteocalcin; Phylloquinone; Point Mutation; Proteins; Prothrombin; Prothrombin Time; Quinones; Rats; Rodents; Toxicology; Toxicology and food chain; Veterinary medicine and animal Health; Vitamin K; Vitamin K - blood; Vitamin K 3 - administration & dosage; Vitamin K Deficiency; vitamin K epoxide reductase; Vitamin K Epoxide Reductases - genetics; Vitamin K Epoxide Reductases - metabolism; vitamin K status; United Kingdom > UK; France; mutation; osteocalcin; vitamin K epoxide reductase; vitamin K status
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu11092076

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 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 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 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.