AFFINITY FOR ALPHA-TOCOPHEROL TRANSFER PROTEIN AS A DETERMINANT OF THE BIOLOGICAL-ACTIVITIES OF VITAMIN-E ANALOGS

alpha-Tocopherol transfer protein (alpha TTP), a product of the gene w hich causes familial isolated vitamin E deficiency, plays an important role in determining the plasma vitamin E level. We examined the struc tural characteristics of vitamin E analogs required for recognition by alpha TTP. Ligand specificity was assessed by evaluating the competit ion of non-labeled vitamin E analogs and alpha-[H-3]tocopherol for tra nsfer between membranes in vitro. Relative affinities (RRR-alpha-tocop herol=100%) calculated from the degree of competition were as follows: beta-tocopherol, 38%; gamma-tocopherol, 9%; delta-tocopherol, 2%; alp ha-tocopherol acetate, 2%; alpha-tocopherol quinone, 2%; SRR-alpha-toc opherol, 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 a nalogs for alpha TTP is one of the critical determinants of their biol ogical activity. (C) 1997 Federation of European Biochemical Societies .