α-Tocopherol transfer protein is not required for the discrimination against γ-tocopherol in vivo but protects it from side-chain degradation in vitro
Article first published online: 13 JAN 2014
© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Molecular Nutrition & Food Research
Volume 58, Issue 5, pages 1052–1060, May 2014
How to Cite
Grebenstein, N., Schumacher, M., Graeve, L. and Frank, J. (2014), α-Tocopherol transfer protein is not required for the discrimination against γ-tocopherol in vivo but protects it from side-chain degradation in vitro. Mol. Nutr. Food Res., 58: 1052–1060. doi: 10.1002/mnfr.201300756
- Issue published online: 22 APR 2014
- Article first published online: 13 JAN 2014
- Manuscript Accepted: 25 NOV 2013
- Manuscript Revised: 16 NOV 2013
- Manuscript Received: 14 OCT 2013
- German Research Foundation. Grant Number: 2478/4-1
- α-Tocopherol transfer protein knockout mouse;
- Cytochrome P450;
- Vitamin E
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.
Methods and 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.
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.