THE ROLE OF METABOLISM IN THE ANTIOXIDANT FUNCTION OF VITAMIN-E

Vitamin E (alpha-tocopherol), the principal chain-breaking antioxidant in biological membranes, prevents toxicant- and carcinogen-induced ox idative damage by trapping reactive oxyradicals. Although alpha-tocoph erol antioxidant reactions appear to be not under direct metabolic con trol, alpha-tocopherol may function through redox cycles, which delive r 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 t hrough redox cycles. Numerous in vitro experiments demonstrate antioxi dant synergism between alpha-tocopherol and ascorbate, reduced glutath ione, NADPH, and cellular electron transport proteins. Nevertheless, e vidence that a one-electron redox cycle regenerates alpha-tocopherol f rom the tocopheroxyl radical is inconclusive. The difficulty of separa ting tocopheroxyl recycling from direct antioxidant actions of other a ntioxidants has complicated interpretation of the available data. A tw o-electron redox cycle involving alpha-tocopherol oxidation to 8a-subs tituted tocopherones followed by tocopherone reduction to alpha-tocoph erol may occur, but would require enzymatic catalysis in vivo. Metabol ism of antioxidant-inactive alpha-tocopheryl esters releases alpha-toc opherol, whereas reductive metabolism of alpha-tocopherylquinone, an a lpha-tocopherol oxidation product, yields alpha-tocopherylhydroquinone , which also may provide antioxidant protection.