Molecular mechanism of cellular uptake and intracellular translocation of alpha-tocopherol: role of tocopherol-binding proteins.
Vitamin E (alpha-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 alpha-tocopherol both in the plasma and different tissues. Mechanisms involved in the preferential accumulation of alpha-tocopherol are not yet well established; however, recent data indicate that both intracellular and membrane alpha-tocopherol-binding proteins may be involved in these processes. A 30 kDa alpha-tocopherol-binding protein (TBP) in the liver cytoplasm is now known to regulate plasma vitamin E concentrations by preferentially incorporating alpha-tocopherol into nascent very low density (VLDL) whereas the 15 kDa TBP may be responsible for intracellular distribution of alpha-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 alpha-tocopherol in preference to the delta- and gamma-tocopherol and may exclusively transport alpha-tocopherol to these intracellular sites. In addition, the presence of a membrane TBP (TBPpm) in tissues may regulate their alpha-tocopherol levels. Activity of erythrocyte TBPpm appears to be reduced in smokers, which may lead to reduced levels of alpha-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 alpha-tocopherol through interactions with these proteins (TBP and TBPpm) is discussed.
Dutta-Roy
A K
AK
Rowett Research Institute, Aberdeen, Scotland, UK.
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001692:Biological Transport; D002352:Carrier Proteins / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D004910:Erythrocyte Membrane / Q000378:metabolism; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D051381:Rats; D012907:Smoking / Q000378:metabolism; D014810:Vitamin E / Q000032:analysis / Q000097:blood / Q000378:metabolism*
D000975:Antioxidants; D002352:Carrier Proteins; C017763:alpha-tocopherol transfer protein; D014810:Vitamin E