Affinity for alpha-tocopherol transfer protein as a determinant of the biological activities of vitamin E analogs

alpha-Tocopherol transfer protein (alphaTTP), a product of the gene which causes familial isolated vitamin E deficiency, plays an important role in determining the plasma vitamin E level. We examined the structural characteristics of vitamin E analogs required for recognition by alphaTTP. Ligand specificity was assessed by evaluating the competition of non-labeled vitamin E analogs and alpha-[3H]tocopherol for transfer between membranes in vitro. Relative affinities (RRR-alpha-tocopherol = 100%) calculated from the degree of competition were as follows: beta-tocopherol, 38%; gamma-tocopherol, 9%; delta-tocopherol, 2%; alpha-tocopherol acetate, 2%; alpha-tocopherol quinone, 2%; SRR-alpha-tocopherol, 11%; alpha-tocotrienol, 12%; trolox, 9%. Interestingly, there was a linear relationship between the relative affinity and the known biological activity obtained from the rat resorption-gestation assay. From these observations, we conclude that the affinity of vitamin E analogs for alphaTTP is one of the critical determinants of their biological activity.