title: α-Tocopherol transfer protein is not required for the discrimination against γ-tocopherol in vivo but protects it from side-chain degradation in vitro.
abstract: METHODS
  The mechanisms underlying the preferential retention of a single compound (α-tocopherol (αT)) of the eight vitamin E compounds in the body are incompletely understood. We hypothesized that vitamin E metabolism and not the hepatic α-tocopherol transfer protein (TTP) is responsible for the discrimination against non-αT congeners.
  
  
  RESULTS
  TTP knockout and wild-type mice (n = 12/group) were fed equimolar concentrations of αT and γ-tocopherol (γT; 50 mg/kg diet each) alone or together with sesamin (2 g/kg diet) for 6 wk. Inhibition of vitamin E metabolism with sesamin, but not TTP knockout, increased γT tissue concentrations. TTP-expressing and TTP-free cells were incubated with equimolar concentrations of αT and γT (25 μmol/L each) with or without sesamin (2 μmol/L). The preferential degradation of γT independently of TTP expression was confirmed and a decrease in the production of the metabolite γ-carboxyethyl hydroxychromanol (CEHC) with increasing TTP expression revealed. Displacing γT from TTP in these cells by incubation with increasing αT concentrations enhanced the secretion of γ-CEHC in TTP-transfected cells, suggesting that TTP might protect γT from β-oxidation.
  
  
  CONCLUSIONS
  We conclude that vitamin E metabolism and not TTP controls γT concentrations in vivo and observed an interaction of TTP with vitamin E metabolism that results in reduced production of the metabolite γ-CEHC.
authors.affiliation: Institute of Biological Chemistry and Nutrition, University of Hohenheim, Stuttgart, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Grebenstein
authors.forename: Monika
authors.initials: M
authors.lastname: Schumacher
authors.forename: Lutz
authors.initials: L
authors.lastname: Graeve
authors.forename: Jan
authors.initials: J
authors.lastname: Frank
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002839:Chromans / Q000378:metabolism; D004149:Dioxoles / Q000494:pharmacology; D005260:Female; D056945:Hep G2 Cells; D006801:Humans; D017705:Lignans / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D006899:Mixed Function Oxygenases / Q000378:metabolism; D010084:Oxidation-Reduction; D011422:Propionates / Q000378:metabolism; D024502:alpha-Tocopherol / Q000494:pharmacology; D024504:gamma-Tocopherol / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D002352:Carrier Proteins; D002839:Chromans; D004149:Dioxoles; D017705:Lignans; D011422:Propionates; C017763:alpha-tocopherol transfer protein; C107690:2,7,8-trimethyl-2-(beta-carboxyethyl)-6-hydroxychroman; D024504:gamma-Tocopherol; D006899:Mixed Function Oxygenases; C479073:tocopherol-omega-hydroxylase; D024502:alpha-Tocopherol; C054125:sesamin
keywords: Cytochrome P450; Liver; Tocopherol-ω-hydroxylase; Vitamin E; α-Tocopherol transfer protein knockout mouse