Molecular Mechanism of Cellular Uptake and Intracellular Translocation of α-Tocopherol: Role of Tocopherol-binding Proteins

Vitamin E (α-tocopherol) is a lipid-soluble antioxidant which is present in cellular membranes where it plays an important role in the suppression of free radical-induced lipid peroxidation. There are eight naturally occurring homologues of vitamin E which differ in their structure and in biological activity in vivo and in vitro. Various studies have suggested that the tocopherol distribution system favours the accumulation of α-tocopherol both in the plasma and different tissues. Mechanisms involved in the preferential accumulation of α-tocopherol are not yet well established; however, recent data indicate that both intracellular and membrane α-tocopherol-binding proteins may be involved in these processes. A 30 kDa α-tocopherol-binding protein (TBP) in the liver cytoplasm is now known to regulate plasma vitamin E concentrations by preferentially incorporating α-tocopherol into nascent very low density (VLDL) whereas the 15 kDa TBP may be responsible for intracellular distribution of α-tocopherol. The 30 kDa TBP is unique to the hepatocyte whereas the 15 kDa TBP is present in all major tissues. The 15 kDa TBP specifically binds α-tocopherol in preference to the δ- and γ-tocopherol and may exclusively transport α-tocopherol to these intracellular sites. In addition, the presence of a membrane TBP (TBPpm) in tissues may regulate their α-tocopherol levels. Activity of erythrocyte TBPpm appears to be reduced in smokers, which may lead to reduced levels of α-tocopherol in these cells despite smokers have similar plasma levels of vitamin E as in non-smokers. The current status of the evidence for this directed flow of α-tocopherol through interactions with these proteins (TBP and TBPpm) is discussed.