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.
Hosomi
A
A
Department of Health Chemistry, Faculty of Pharmaceutical Sciences, University of Tokyo, Bunkyo-ku, Japan.
Arita
M
M
Sato
Y
Y
Kiyose
C
C
Ueda
T
T
Igarashi
O
O
Arai
H
H
Inoue
K
K
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D008079:Lipoproteins, VLDL / Q000378:metabolism; D008081:Liposomes; D008099:Liver / Q000378:metabolism; D008297:Male; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology*
D000975:Antioxidants; D002352:Carrier Proteins; D008079:Lipoproteins, VLDL; D008081:Liposomes; C017763:alpha-tocopherol transfer protein; D014810:Vitamin E