Formation of 3-hydroxy-2,3-dihydrovitamin K1 in vivo: relationship to vitamin K epoxide reductase and warfarin resistance.
Hydroxy vitamin K [3(2)-hydroxy-2,3- dihydrovitamin K1] has been identified as a quantitatively important metabolite of injected vitamin K epoxide in vivo. The metabolite has been isolated and identified by comparison of its UV, mass spectra and high-performance liquid chromatography (HPLC) retention times with those of synthetic standards, and by its characteristic conversion to vitamin K quinone on treatment with the base triethylamine. This metabolite is formed from the vitamin K epoxide, not from the vitamin K quinone and can represent up to 3.5% of dose and 13% of hexane-extractable metabolites present in liver 1 hour after injection of 330 micrograms vitamin K1 epoxide per kilogram body weight. It is formed in both normal and warfarin-resistant rat strains, but to a significantly greater extent in the latter. Unlike the hydroxy vitamin K formed by warfarin-resistant rat liver microsomes in vitro, the metabolite formed from racemic vitamin K epoxide in vivo was not optically active, nor was its formation inhibited by coumarin anticoagulants under conditions that completely blocked vitamin K epoxide reduction in vivo. On this basis, hydroxy vitamin K formation in vivo differs from its formation in vitro; it is not a product of vitamin K epoxide reductase in vivo, but of some other possibly non-enzymatic reaction.
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004351:Drug Resistance; D008099:Liver / Q000378:metabolism; D008297:Male; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D051381:Rats; D014812:Vitamin K / Q000031:analogs & derivatives* / Q000378:metabolism; D010837:Vitamin K 1 / Q000031:analogs & derivatives / Q000378:metabolism; D014813:Vitamin K Deficiency / Q000378:metabolism; D064417:Vitamin K Epoxide Reductases; D014859:Warfarin / Q000494:pharmacology*
D014812:Vitamin K; C016186:vitamin K1 oxide; D014859:Warfarin; C045267:3-hydroxy-2-methyl-3-phytyl-2,3-dihydronaphthoquinone; D010837:Vitamin K 1; D006899:Mixed Function Oxygenases; D064417:Vitamin K Epoxide Reductases