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.

Antioxidant activities of natural vitamin E formulations

Naguib Y, Hari SP, Passwater R Jr, Huang D.

J Nutr Sci Vitaminol (Tokyo). 2003 Aug;49(4):217-20.

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.

2,7,8-Trimethyl-2-(beta-carboxyethyl)-6-hydroxychroman (gamma-CEHC), a metabolite of gamma-tocopherol and gamma-tocotrienol, was identified as a new endogenous natriuretic factor. However, gamma-tocopherol and gamma-tocotrienol, both precursors of gamma-CEHC, have never directly been observed to have natriuretic potency. Thus, we investigated whether gamma-tocotrienol could cause natriuresis and diuresis in rats. The rats were divided into two groups that were given a control or a high-sodium diet for 4 weeks, and then subdivided into placebo and gamma-tocotrienol subgroups given only corn oil-removed vitamin E and oil supplemented with gamma-tocotrienol, respectively. After oral administration of three experimental doses, rat urine was collected and gamma-CEHC, urine volume, sodium, and potassium content were determined. Only in rats given a high-NaCl diet did gamma-tocotrienol accelerate and increase sodium excretion, showing no effect on potassium excretion. Sodium excretion in the high-NaCl group given gamma-tocotrienol was 5.06 +/- 2.70 g/day, and in the control group given gamma-tocotrienol, 0.11 +/- 0.06 g/day. Furthermore, gamma-tocotrienol affected urine volume in the specific condition of high-NaCl body stores and gamma-tocotrienol supplementation. In this study, we found that gamma-tocotrienol, one of the natural vitamin E homologs, stimulates sodium excretion in vivo, suggesting that gamma-tocotrienol possesses a hormone-like natriuretic function.