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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. Author: Grebenstein N, Schumacher M, Graeve L, Frank J. Journal: Mol Nutr Food Res; 2014 May; 58(5):1052-60. PubMed ID: 24420818. Abstract: SCOPE: 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. 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.[Abstract] [Full Text] [Related] [New Search]