Alpha-tocopherol transfer protein (alpha-TTP) is a liver protein responsible for the selective retention of alpha-tocopherol from dietary vitamin E, which is a mixture of alpha, beta, gamma, and delta-tocopherols and the corresponding tocotrienols. The alpha-TTP-mediated transfer of alpha-tocopherol into nascent VLDL is the major determinant of plasma alpha-tocopherol levels in humans. Mutations in the alpha-TTP gene have been detected in patients suffering from low plasma alpha-tocopherol and ataxia with isolated vitamin E deficiency (AVED). The crystal structure of alpha-TTP reveals two conformations. In its closed tocopherol-charged form, a mobile helical surface segment seals the hydrophobic binding pocket. In the presence of detergents, an open conformation is observed, which probably represents the membrane-bound form. The selectivity of alpha-TTP for RRR-alpha-tocopherol is explained from the van der Waals contacts occurring in the lipid-binding pocket. Mapping the known mutations leading to AVED onto the crystal structure shows that no mutations occur directly in the binding pocket.
The antioxidant activities of natural d-alpha-tocopherol, mixed tocopherols and tocotrienols, and formulations comprising all forms of vitamin E, providing 400 IU, were determined employing an improved oxygen radical absorbance capacity (ORAC) assay using fluorescein (FL) as the fluorescent probe, randomly methylated beta-cyclodextrin (RMCD), 2,2′-azobis(2-amidino-propane)dihydrochloride (AAPH) as the peroxyl radical generator, and Trolox as the standard in 75 mM phosphate buffer. The antioxidant activities, expressed in micromol Trolox equivalent per gram, of d-alpha-tocopherol (87%), mixed tocopherols (70%), and tocotrienols (30%) were found to be 1,293, 1,948, and 1,229, respectively. Some of the vitamin E formulations showed antioxidant activities superior to d-alpha-tocopherol.