Phylloquinone and menaquinone-4 distribution in rats: synthesis rather than uptake determines menaquinone-4 organ concentrations.
To clarify the origin of organ menaquinone-4 (MK-4), the distributions of phylloquinone and MK-4 were investigated in rats fed diets containing phylloquinone, MK-4 or menadione (1.1, 2.2 and 31 mumol/kg diet, respectively, 6 rats per group). Warfarin (2 x 1 mg/kg subcutaneously) was given (3 rats per group) to study the effect of vitamin K cycle blockage. In rats fed phylloquinone the vitamin accumulated mainly in liver and heart. Additionally, the diet resulted in significantly higher organ MK-4 concentrations compared with the vitamin K-deficient controls. The epoxide of MK-4 also was significantly higher in some organs. The MK-4 diet increased MK-4 concentration primarily in the heart, liver and lung. Rats fed menadione had significantly higher MK-4 and MK-4 epoxide concentrations in all organs examined. The greatest accumulations were in nonhepatic organs, particularly the pancreas, salivary gland and brain. Generally, liver and plasma had low MK-4 concentrations. Warfarin treatment lowered significantly the MK-4 concentrations, whereas MK-4 epoxide accumulated. The study shows the following: 1) dietary phylloquinone is accumulated mainly in the heart and liver, 2) the MK-4 accumulation in nonhepatic organs is due to synthesis rather than uptake and 3) MK-4 rather than phylloquinone may be the functional vitamin in nonhepatic organs.
Thijssen
H H
HH
Department of Pharmacology, University of Limburg, Maastricht, The Netherlands.
Drittij-Reijnders
M J
MJ
Fischer
M A
MA
D000818:Animals; D001923:Brain Chemistry; D008099:Liver / Q000737:chemistry* / Q000378:metabolism; D008168:Lung / Q000737:chemistry* / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000737:chemistry* / Q000378:metabolism; D010179:Pancreas / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012469:Salivary Glands / Q000737:chemistry / Q000378:metabolism; D014812:Vitamin K / Q000008:administration & dosage / Q000032:analysis* / Q000096:biosynthesis* / Q000378:metabolism / Q000494:pharmacology; D010837:Vitamin K 1 / Q000008:administration & dosage / Q000032:analysis* / Q000378:metabolism; D014813:Vitamin K Deficiency / Q000378:metabolism; D014859:Warfarin / Q000494:pharmacology
D014812:Vitamin K; D014859:Warfarin; D010837:Vitamin K 1