Homologous metabolic and gene activating routes for vitamins E and K.
Vitamins E and K share structurally related side chains and are degraded to similar final products. For vitamin E the mechanism has been elucidated as initial omega-hydroxylation and subsequent beta-oxidation. For vitamin K the same mechanism can be suggested analogously. omega-Hydroxylation of vitamin E is catalyzed by cytochrome p450 enzymes, which often are induced by their substrates themselves via the activation of the nuclear receptor PXR. Vitamin E is able to induce CYP3A-forms and to activate a PXR-driven reporter gene. It is shown here that K-type vitamins are also able to activate PXR. A ranking showed that compounds with an unsaturated side chain were most effective, as are tocotrienols and menaquinone-4 (vitamin K(2)), which activated the reporter gene 8-10-fold. Vitamers with a saturated side chain, like tocopherols and phylloquinone were less active (2-5-fold activation). From the fact that CYPs commonly responsible for the elimination of xenobiotics are involved in the metabolism of fat-soluble vitamins and the ability of the vitamins to activate PXR it can be concluded that supranutritional amounts of these vitamins might be considered as foreign.
Department of Vitamins and Atherosclerosis, German Institute of Human Nutrition, University of Potsdam, Arthur-Scheunert-Allee 114-116, Bergholz-Rehbruecke D-14558, Germany.
Nico
N
Landes
Marc
M
Birringer
Regina
R
Brigelius-Flohé
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004790:Enzyme Induction; D017930:Genes, Reporter; D006801:Humans; D006900:Hydroxylation; D015394:Molecular Structure; D010084:Oxidation-Reduction; D011987:Receptors, Steroid / Q000378:metabolism; D014451:Ubiquinone / Q000378:metabolism; D014810:Vitamin E / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D014812:Vitamin K / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D015262:Xenobiotics / Q000378:metabolism
D011987:Receptors, Steroid; D015262:Xenobiotics; D014812:Vitamin K; D014451:Ubiquinone; D014810:Vitamin E; D003577:Cytochrome P-450 Enzyme System