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-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 K1 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.
Craciun
A M
AM
Department of Biochemistry, Cardiovascular Research Institute, Maastricht University, The Netherlands.
Groenen-van Dooren
M M
MM
Thijssen
H H
HH
Vermeer
C
C
D015110:4-Hydroxycoumarins / Q000494:pharmacology*; D000042:Absorption; D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D001777:Blood Coagulation / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D008297:Male; D011516:Prothrombin / Q000096:biosynthesis*; D051381:Rats; D011917:Rats, Inbred Lew; D014812:Vitamin K / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000494:pharmacology*; D010837:Vitamin K 1 / Q000494:pharmacology; D024482:Vitamin K 2 / Q000031:analogs & derivatives*; D014813:Vitamin K Deficiency / Q000097:blood* / Q000188:drug therapy* / Q000378:metabolism
D015110:4-Hydroxycoumarins; D000925:Anticoagulants; D024482:Vitamin K 2; D014812:Vitamin K; C030814:menatetrenone; C073355:menaquinone 9; D010837:Vitamin K 1; D011516:Prothrombin; C013418:bromfenacoum