Homologous metabolic and gene activating routes for vitamins E and K

Mol Aspects Med. 2003 Dec;24(6):337-44. doi: 10.1016/s0098-2997(03)00029-3.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cytochrome P-450 Enzyme System / metabolism
  • Enzyme Induction
  • Genes, Reporter
  • Humans
  • Hydroxylation
  • Molecular Structure
  • Oxidation-Reduction
  • Receptors, Steroid / metabolism
  • Ubiquinone / metabolism
  • Vitamin E / chemistry
  • Vitamin E / genetics*
  • Vitamin E / metabolism*
  • Vitamin K / chemistry
  • Vitamin K / genetics*
  • Vitamin K / metabolism*
  • Xenobiotics / metabolism


  • Receptors, Steroid
  • Xenobiotics
  • Vitamin K
  • Ubiquinone
  • Vitamin E
  • Cytochrome P-450 Enzyme System