Nutritional vitamin K-intake and urinary gamma-carboxyglutamate excretion in the rat.
Using the rat as an experimental animal model we have found that prothrombin synthesis reaches its maximal level at a relatively low dietary vitamin K intake. At still higher vitamin K intakes, however, the urinary Gla-excretion was substantially increased, showing a different vitamin K requirement for liver and extrahepatic tissues. The increased urinary Gla-excretion was found for both phylloquinone and menaquinone-4, but not for menaquinone-8, which questions the bioavailability of higher menaquinones for extrahepatic tissues. A discrepancy was found between effects of nutritional vitamin K-deficiency and treatment with a vitamin K-antagonist (brodifacoum). With both regimens plasma prothrombin rapidly decreased to well below 10% of the starting values, but in case of K-deficiency urinary Gla had hardly decreased in 7 days, whereas after 3 days of brodifacoum treatment Gla-excretion had decreased to 17% of the starting values. An explanation for this observation is that prothrombin procoagulant activity does not decrease proportional to the prothrombin Gla-content, but that a wide range of undercarboxylated prothrombins have lost nearly all activity. During vitamin K-deficiency the remaining low levels of vitamin K would mainly give rise to undercarboxylated prothrombin, whereas during brodifacoum treatment only non-carboxylated prothrombin is formed. It seems plausible that in the latter case the urinary Gla originates from proteins with long half-life times, such as the bone Gla-proteins.
Craciun
A M
AM
Cardiovascular Research Institute Maastricht, University of Limburg, The Netherlands.
Groenen-van Dooren
M M
MM
Vermeer
C
C
D015055:1-Carboxyglutamic Acid / Q000652:urine*; D015110:4-Hydroxycoumarins / Q000494:pharmacology; D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage; D004032:Diet; D004305:Dose-Response Relationship, Drug; D008297:Male; D011516:Prothrombin / Q000032:analysis* / Q000096:biosynthesis; D051381:Rats; D014812:Vitamin K / Q000008:administration & dosage* / Q000032:analysis / Q000037:antagonists & inhibitors; D014813:Vitamin K Deficiency / Q000097:blood / Q000652:urine
D015110:4-Hydroxycoumarins; D000925:Anticoagulants; D014812:Vitamin K; D015055:1-Carboxyglutamic Acid; D011516:Prothrombin; C013418:bromfenacoum