Vitamin E requirements, transport, and metabolism: role of alpha-tocopherol-binding proteins.
1994
Dutta Roy A.K. | Gordon M.J. | Campbell F.M. | Duthie G.G. | James W.P.T.
Vitamin E (RRR-alpha-tocopherol) is a lipid-soluble antioxidant that is present in the membranes of intracellular organelles. There it plays an important role in the suppression of free radical-induced lipid peroxidation. There are eight naturally occurring homologues of vitamin E that differ in their structure and in biological activity in vivo and in vitro. Although gamma-tocopherol is a more effective free radical scavenger than alpha-tocopherol in vitro, the reverse is true in vivo, suggesting that the tocopherol distribution systems favor the localization of alpha-tocopherol at the sites where it is required. Vitamin E is transported in plasma primarily by lipoproteins, but little is known of how it is transported intracellularly. A 30 kDa alpha-tocopherol-binding protein in the liver cytoplasm may regulate plasma vitamin E concentrations by preferentially incorporating the vitamin E homologue, RRR-alpha-tocopherol (alpha-tocopherol), into nascent very low density lipoproteins. However, this alpha-tocopherol-binding protein is unique to the hepatocyte, whereas alpha-tocopherol is present in the cells of all major tissues. Moreover alpha-tocopherol accumulates at those sites within the cell where oxygen radical production is greatest and thus where it is most required; in the membranes of heavy mitochondria, light mitochondria, and endoplasmic reticulum. This raises the question of how the lipid-soluble alpha-tocopherol is transported intracellularly in different tissues. We have identified a new alpha-tocopherol-binding protein of molecular mass 14.2 kDa in the cytosol of heart and liver. This protein specifically binds alpha-tocopherol in preference to the delta- and gamma-homologues but does not bind oleate. Studies on immunoreactivity and ligand specifcity of the protein suggest that it is not a fatty acid-binding protein. The 14.2 kDa alpha-tocopherol-binding protein stimulates the transfer of alpha-tocopherol from liposomes to mitochondria in vitro.
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