α-Tocopherol transfer protein is not required for the discrimination against γ-tocopherol in vivo but protects it from side-chain degradation in vitro

ScopeThe mechanisms underlying the preferential retention of a single compound (-tocopherol (T)) of the eight vitamin E compounds in the body are incompletely understood. We hypothesized that vitamin E metabolism and not the hepatic -tocopherol transfer protein (TTP) is responsible for the discrimination against non-T congeners. Methods and resultsTTP knockout and wild-type mice (n = 12/group) were fed equimolar concentrations of T and -tocopherol (T; 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 T tissue concentrations. TTP-expressing and TTP-free cells were incubated with equimolar concentrations of T and T (25 mol/L each) with or without sesamin (2 mol/L). The preferential degradation of T independently of TTP expression was confirmed and a decrease in the production of the metabolite -carboxyethyl hydroxychromanol (CEHC) with increasing TTP expression revealed. Displacing T from TTP in these cells by incubation with increasing T concentrations enhanced the secretion of -CEHC in TTP-transfected cells, suggesting that TTP might protect T from -oxidation. ConclusionsWe conclude that vitamin E metabolism and not TTP controls T concentrations in vivo and observed an interaction of TTP with vitamin E metabolism that results in reduced production of the metabolite -CEHC.