Affinity for α‐tocopherol transfer protein as a determinant of the biological activities of vitamin E analogs

Abstract

α‐Tocopherol transfer protein (αTTP), 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 αTTP. Ligand specificity was assessed by evaluating the competition of non‐labeled vitamin E analogs and α‐[3 H]tocopherol for transfer between membranes in vitro. Relative affinities (RRR‐α‐tocopherol=100%) calculated from the degree of competition were as follows: β‐tocopherol, 38%; γ‐tocopherol, 9%; δ‐tocopherol, 2%; α‐tocopherol acetate, 2%; α‐tocopherol quinone, 2%; SRR‐α‐tocopherol, 11%; α‐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 αTTP is one of the critical determinants of their biological activity.