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.
Landes
Nico
N
Department of Vitamins and Atherosclerosis, German Institute of Human Nutrition, University of Potsdam, Arthur-Scheunert-Allee 114-116, Bergholz-Rehbruecke D-14558, Germany.
Birringer
Marc
M
Brigelius-Flohé
Regina
R
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