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

TLDR

Alpha‑Tocopherol transfer protein (alphaTTP), a product of the gene responsible for familial isolated vitamin E deficiency, regulates plasma vitamin E levels. The study aimed to identify the structural features of vitamin E analogs that enable recognition by alphaTTP. Ligand specificity was evaluated by measuring competition between unlabeled analogs and alpha‑[3H]tocopherol for membrane‑mediated transfer in vitro. Relative affinities of analogs ranged from 2 % to 38 %, and a linear correlation with biological activity in a rat resorption‑gestation assay showed that alphaTTP affinity is a critical determinant of their biological effects.

Abstract

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.