Induction of prothrombin synthesis by K-vitamins compared in vitamin K-deficient and in brodifacoum-treated rats

Vitamin K is a group name for a number of prenylated 2-methyl-1,4-naphtoquinones, which may differ in their ability to function as a cofactor for prothrombin biosynthesis. To quantify the bioactivity of different forms of vitamin K, two experimental animal systems are frequently used: vitamin K-defi...

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Published in:Biochimica et biophysica acta 1998-03, Vol.1380 (1), p.75-81
Main Authors: Crāciun, A.M, Groenen-van Dooren, M.M.C.L, Thijssen, H.H.W, Vermeer, C
Format: Article
Language:English
Subjects:
4-Hydroxycoumarins - pharmacology
Absorption
Animals
Anticoagulants - pharmacology
biosynthesis
Blood coagulation
Blood Coagulation - drug effects
Blood Coagulation - physiology
Coumarin
Disease Models, Animal
Male
Menaquinone
menaquinones
Oral anticoagulant
Phylloquinone
prothrombin
Prothrombin - biosynthesis
Rats
Rats, Inbred Lew
vitamin deficiencies
Vitamin K
Vitamin K - administration & dosage
Vitamin K - analogs & derivatives
Vitamin K - pharmacokinetics
Vitamin K - pharmacology
Vitamin K 1 - pharmacology
Vitamin K 2 - analogs & derivatives
Vitamin K Deficiency - blood
Vitamin K Deficiency - drug therapy
Vitamin K Deficiency - metabolism
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Summary:Vitamin K is a group name for a number of prenylated 2-methyl-1,4-naphtoquinones, which may differ in their ability to function as a cofactor for prothrombin biosynthesis. To quantify the bioactivity of different forms of vitamin K, two experimental animal systems are frequently used: vitamin K-deficient rats and anticoagulated rats. In this paper both models are compared, and it is shown that the results obtained depend on the model used. The main reason for this discrepancy is the difference in recycling of vitamin K-epoxide, which results in a 500 times higher vitamin K requirement in anticoagulated rats. Absorption and hepatic accumulation of long chain menaquinones seem to be restricted to a maximum, whereas also the lipophilic nature of long chain menaquinones may hamper the quinone–quinol reduction in anticoagulated animals. If these data may be extrapolated to patients, food items rich in K 1 and MK-4 would be expected to influence the stability of oral anticoagulation to a much larger extent than food items primarily containing higher menaquinones.
ISSN:0304-4165
0006-3002
1872-8006
1878-2434
DOI:10.1016/S0304-4165(97)00134-7