CONVERSION OF DIETARY PHYLLOQUINONE TO TISSUE MENAQUINONE-4 IN RATS IS NOT DEPENDENT ON GUT BACTERIA

The ability of male rats to accumulate menaquinone-4 (MK-4) in tissues when fed a vitamin K-deficient diet supplemented with intraperitoneal phylloquinone (K) as the sole source of vitamin K for 14 d was assess ed, In both conventionally housed controls and gnotobiotic rats, suppl ementation with the equivalent of 1500 mu g vitamin K/kg diet increase d (P < 0.001) tissue MK-4 concentrations above those of controls fed a vitamin K-deficient diet MK-4 concentrations were similar to 5 ng/g ( 11 pmol/g) in liver, 14 ng/g in heart, 17 ng/g in kidney, 50 ng/g in b rain and 250 ng/g in mandibular salivary glands of gnotobiotic rats. M K-4 concentrations in conventionally housed rats were higher than in g notobiotic rats in heart (P < 0.01), brain (P < 0.01) and kidney (P < 0.05) but lower in salivary gland (P < 0.05). Cultures of a kidney-der ived cell line (293) converted K to the epoxide of MK-4 in a manner th at was dependent on both time of incubation and concentration of vitam in K in the media, A liver-derived cell line (H-35) was less active in carrying out this conversion, These data offer conclusive proof that the tissue-specific formation of MK-4 from K is a metabolic transforma tion that does not require bacterial transformation to menadione as an intermediate In the process.