American Journal of Clinical Nutrition, Vol 27, 987-994, Copyright © 1974 by The American Society for Clinical Nutrition, Inc.

Inhibition of membrane adenosine triphosphatase by alpha-tocopherol and its derivatives

¹ Lecturer of Biochemistry, Department of Toxicology, Tokyo Metropolitan Institute of Health
² Professor of Biochemistry, Department of Toxicology, Tokyo Metropolitan Institute of Health
³ Head of Biochemistry and Pharmacology, Department of Toxicology, Tokyo Metropolitan Institute of Health
⁴ Research Director, Eisai Co. Ltd., Bunkyo, Tokyo

Although it has been reported that -tocopherol acts as a lipid antioxidant, that it inhibits various enzymes involved in biological oxidation, and that -tocopherol stabilizes the cell membrane, the exact function of the vitamin in the cell membrane is still unknown. Using partially and highly purified Na,K-ATPase preparations, the effects of tocopherols and their derivatives were tested as sonicated suspensions in water. -Tocopherol and -tocopherylquinone inhibited the Na,K-ATPase with one-half maximal inhibition at 5.7 x 10^–5M and 3.1 x 10^–5M, respectively (near the physiological vitamin E concentration in blood, 3 x 10^–5M). Other tocopherol derivatives and fat-soluble vitamins did not show such strong inhibition. For example, the K_i value of -tocopheryl acetate was 50 times greater than that of free -tocopherol. BHT, cysteine, and DTT did not affect the inhibition. Ca ATPase from muscle was similarly inhibited. On the other hand, ouabain-insensitive ATPase from rabbit brain and liver was slightly affected. There seemed to be no effect on acetylcholinesterase from human erythrocytes, and little or no effect on 5-nucleotidase and G6Pase from rabbit brain. Some kinetical examination of -tocopherol and -tocopherylquinone was performed.