Biomaterial Database

Vitamin E and drug metabolism. 2003

Regina Brigelius-Flohé

Department of Vitamins and Atherosclerosis, German Institute of Human Nutrition, University of Potsdam, Potsdam-Rehbruecke, Germany. flohe@mail.dife.de

Tocopherols and tocotrienols are metabolized by side chain degradation initiated by cytochrome P450 (CYP)-catalyzed omega-hydroxylation followed by beta-oxidation. Whereas alpha-tocopherol is only poorly metabolized, high amounts of the final products, carboxyethyl hydroxychroman (CEHC), are found from other tocols in HepG2 cells and in human urine. CYP3A4 and CYP4F2 were suggested to be involved in tocopherol degradation. CYP3A4 metabolizes most of the drugs and is induced by many of its substrates via the activation of the pregnane X receptor (PXR). Also tocopherols and in particular tocotrienols induce the expression of a PXR-driven reporter gene and the expression of endogenous CYP3A4 and CYP3A5 which is supported by sporadic publications spread over the last 30 years. The potential interference of vitamin E with drug metabolism is discussed in the light of related complications evoked by herbal remedies.

UI	MeSH Term	Description	Entries
D008956	Models, Chemical	Theoretical representations that simulate the behavior or activity of chemical processes or phenomena; includes the use of mathematical equations, computers, and other electronic equipment.	Chemical Models,Chemical Model,Model, Chemical
D003577	Cytochrome P-450 Enzyme System	A superfamily of hundreds of closely related HEMEPROTEINS found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (MIXED FUNCTION OXYGENASES). In animals, these P-450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (BIOTRANSFORMATION). They are classified, according to their sequence similarities rather than functions, into CYP gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the CYP1, CYP2, and CYP3 gene families are responsible for most drug metabolism.	Cytochrome P-450,Cytochrome P-450 Enzyme,Cytochrome P-450-Dependent Monooxygenase,P-450 Enzyme,P450 Enzyme,CYP450 Family,CYP450 Superfamily,Cytochrome P-450 Enzymes,Cytochrome P-450 Families,Cytochrome P-450 Monooxygenase,Cytochrome P-450 Oxygenase,Cytochrome P-450 Superfamily,Cytochrome P450,Cytochrome P450 Superfamily,Cytochrome p450 Families,P-450 Enzymes,P450 Enzymes,Cytochrome P 450,Cytochrome P 450 Dependent Monooxygenase,Cytochrome P 450 Enzyme,Cytochrome P 450 Enzyme System,Cytochrome P 450 Enzymes,Cytochrome P 450 Families,Cytochrome P 450 Monooxygenase,Cytochrome P 450 Oxygenase,Cytochrome P 450 Superfamily,Enzyme, Cytochrome P-450,Enzyme, P-450,Enzyme, P450,Enzymes, Cytochrome P-450,Enzymes, P-450,Enzymes, P450,Monooxygenase, Cytochrome P-450,Monooxygenase, Cytochrome P-450-Dependent,P 450 Enzyme,P 450 Enzymes,P-450 Enzyme, Cytochrome,P-450 Enzymes, Cytochrome,Superfamily, CYP450,Superfamily, Cytochrome P-450,Superfamily, Cytochrome P450
D004364	Pharmaceutical Preparations	Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or formulation of the finished dosage form.	Drug,Drugs,Pharmaceutical,Pharmaceutical Preparation,Pharmaceutical Product,Pharmaceutic Preparations,Pharmaceutical Products,Pharmaceuticals,Preparations, Pharmaceutical,Preparation, Pharmaceutical,Preparations, Pharmaceutic,Product, Pharmaceutical,Products, Pharmaceutical
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D024505	Tocopherols	A collective name for a group of closely related lipids that contain substitutions on the 2H-1-benzopyran-6-ol nucleus and a long hydrocarbon chain of isoprenoid units. They are antioxidants by virtue of the phenolic hydrogen. Tocopherols react with the most reactive form of oxygen and protect unsaturated fatty acids from oxidation.	Tocopherol,Abortosan,Antioxidans E-Hevert,Aquasol E,Auxina E,Bio E,Biopto-E,Biosan,Bioweyxin,Dal-E,Davitamon,Dermorelle,Detulin,E Vitamin E,E-Mulsin,E-Vicotrat,E-Vitamin-Ratiopharm,E-ferol,EUNOVA Vitamin E,Ecoro,Elex Verla,Embial,Ephynal,Eplonat,Equivit E,Eusovit,Evion,Hydrovit E,Lasar,Malton E,Micorvit E,Mowivit Vitamin E,Puncto E,Richtavit E,Sanavitan S,Snow-E Muscle, Energy & Feritility,Spondyvit,Tocolion,Tocopa,Tocopharm,Tocopherol Bayer,Tocovital,Togasan Vitamin E,Unique E,Uno-Vit,Vibolex,Vit E hydrosol,Vit. E Stada,Vita-E,Vita-Plus E,Vitagutt Vitamin E,Vitamin E AL,Vitamin E Natur,Vitamin E Sanum,Vitamin E Suspension,Vitamin E-mp,Vitamin-E Dragees,Vitamin-E EVI-MIRALE,Vitamine E GNR,Vitazell,Dal E,E Mulsin,E Vicotrat,Uno Vit,UnoVit,Vita E,Vita Plus E,VitaE,VitaPlus E,Vitamin E Dragees,Vitamin E EVI MIRALE,Vitamin E mp,Vitamin E, Mowivit,Vitamin E, Togasan,Vitamin E, Vitagutt,Vitamin Emp,VitaminE EVIMIRALE
D024508	Tocotrienols	Natural analogs of TOCOPHEROLS exhibiting antioxidant activity. These tocol derivatives and isomers contain a benzopyran ring and an unsaturated isoprenoid side chain.	Tocotrienol