Vitamin E requirements, transport, and metabolism: Role of α-tocopherol-binding proteins

Vitamin E (RRR-α-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 γ-tocopherol is a more effective free radical scavenger than α-tocopherol in vitro, the reverse is true in vivo, suggesting that the tocopherol distribution systems favor the localization of α-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 α-tocopherol-binding protein in the liver cytoplasm may regulate plasma vitamin E concentrations by preferentially incorporating the vitamin E homologue, RRR-α-tocopherol (α-tocopherol), into nascent very low density lipoproteins. However, this α-tocopherol-binding protein is unique to the hepatocyte, whereas α-tocopherol is present in the cells of all major tissues. Moreover α-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 α-tocopherol is transported intracellularly in different tissues. We have identified a new α-tocopherol-binding protein of molecular mass 14.2 kDa in the cytosol of heart and liver. This protein specifically binds α-tocopherol in preference to the δ- and γ-homologues but does not bind oleate. Studies on immunoreactivity and ligand specificity of the protein suggest that it is not a fatty acid-binding protein. The 14.2 kDa α-tocopherol-binding protein stimulates the transfer of α-tocopherol from liposomes to mitochondria in vitro by 8 to 10 fold. We suggest that this low molecular mass TBP may be responsible for the intracellular transport and distribution of α-tocopherol in the tissues.