The Role of Metabolism in the Antioxidant Function of Vitamin E

Abstract

Vitamin E (alpha-tocopherol), the principal chain-breaking antioxidant in biological membranes, prevents toxicant- and carcinogen-induced oxidative damage by trapping reactive oxyradicals. Although alpha-tocopherol antioxidant reactions appear to be not under direct metabolic control, alpha-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 alpha-tocopherol and evaluates the experimental evidence for the linkage of alpha-tocopherol turnover to cellular metabolism through redox cycles. Numerous in vitro experiments demonstrate antioxidant synergism between alpha-tocopherol and ascorbate, reduced glutathione, NADPH, and cellular electron transport proteins. Nevertheless, evidence that a one-electron redox cycle regenerates alpha-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 alpha-tocopherol oxidation to 8a-substituted tocopherones followed by tocopherone reduction to alpha-tocopherol may occur, but would require enzymatic catalysis in vivo. Metabolism of antioxidant-inactive alpha-tocopheryl esters releases alpha-tocopherol, whereas reductive metabolism of alpha-tocopherylquinone, an alpha-tocopherol oxidation product, yields alpha-tocopherylhydroquinone, which also may provide antioxidant protection.