The Role of Metabolism in the Antioxidant Function of Vitamin E

Abstract

Vitamin E (α-tocopherol), the principal chain-breaking antioxidant in biological membranes, prevents toxicant- and carcinogen-induced oxidative damage by trapping reactive oxyradicals. Although α-tocopherol antioxidant reactions appear to be not under direct metabolic control, α-tocopherol may function through redox cycles, which deliver reducing equivalents for antioxidant reactions and link antioxidant function to cellular metabolism. This review describes the antioxidant chemistry of α-tocopherol and evaluates the experimental evidence for the linkage of α-tocopherol turnover to cellular metabolism through redox cycles. Numerousin vitro experiments demonstrate antioxidant synergism between α-tocopherol and ascorbate, reduced glutathione, NADPH, and cellular electron transport proteins. Nevertheless, evidence that a one-electron redox cycle regenerates α-tocopherol from the tocopheroxyl radical is inconclusive. The difficulty of separating tocopheroxyl recycling from direct antioxidant actions of other antioxidants has complicated interpretation of the available data. A two-electron redox cycle involving α-tocopherol oxidation to 8a-substituted tocopherones followed by tocopherone reduction to α-tocopherol may occur, but would require enzymatic catalysisin vivo. Metabolism of antioxidant-inactive α-tocopheryl esters releases α-tocopherol, whereas reductive metabolism of α-tocopherylquinone, an α-tocopherol oxidation product, yields α-tocopherylhydroquinone, which also may provide antioxidant protection.

Key Words:

• α-tocopherol
• vitamin E
• ascorbic acid
• vitamin C
• glutathione
• free radicals
• lipid peroxidation
• redox cycles