Comparative distribution, metabolism, and utilization of phylloquinone and menaquinone-9 in rat liver.

The liver of most species contains a spectrum of bacterially produced menaquinone homologs as well as the major dietary form of vitamin K, phylloquinone. The relative utilization of phylloquinone and menaquinone-9 (MK-9) as substrates for the microsomal vitamin K-dependent gamma-glutamyl carboxylase was determined in a rat model. Vitamin K 2,3-epoxide, the co-product of the carboxylation reaction, is recycled to the quinone form of the vitamin by a microsomal vitamin K epoxide reductase. This enzyme activity was blocked by warfarin administration, and the appearance of the hepatic epoxides of phylloquinone and MK-9 was determined as a measure of their utilization by the carboxylase. When the liver contained equimolar amounts of phylloquinone and MK-9, four times as much phylloquinone epoxide as MK-9 epoxide was present in the liver 1 hr after warfarin administration. These data suggest that hepatic MK-9 is not as efficiently utilized as phylloquinone. The data obtained have also demonstrated a previously unrecognized difference in phylloquinone and menaquinone metabolism. MK-9 epoxide, and to a lesser extent MK-9, was preferentially localized in the mitochondria, while higher concentrations of phylloquinone were found in the microsomes.