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We examined how \u03b3-tocopherol (\u03b3T), the principal form of vitamin E in the United States diet, and \u03b1-tocopherol (\u03b1T), the major form in supplements, protect against peroxynitrite-induced lipid oxidation. Lipid hydroperoxide formation in liposomes (but not isolated low-density lipoprotein) exposed to peroxynitrite or the \u00b7NO and O\n                    <jats:sub>2\u2a2a<\/jats:sub>\n                    generator SIN-1 (3-morpholinosydnonimine) was inhibited more effectively by \u03b3T than \u03b1T. More importantly, nitration of \u03b3T at the nucleophilic 5-position, which proceeded in both liposomes and human low density lipoprotein at yields of \u224850% and \u224875%, respectively, was not affected by the presence of \u03b1T. These results suggest that despite \u03b1T\u2019s action as an antioxidant \u03b3T is required to effectively remove the peroxynitrite-derived nitrating species. We postulate that \u03b3T acts\n                    <jats:italic>in vivo<\/jats:italic>\n                    as a trap for membrane-soluble electrophilic nitrogen oxides and other electrophilic mutagens, forming stable carbon-centered adducts through the nucleophilic 5-position, which is blocked in \u03b1T. Because large doses of dietary \u03b1T displace \u03b3T in plasma and other tissues, the current wisdom of vitamin E supplementation with primarily \u03b1T should be reconsidered.\n                  <\/jats:p>","DOI":"10.1073\/pnas.94.7.3217","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:31:39Z","timestamp":1027679499000},"page":"3217-3222","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":445,"title":["\u03b3-Tocopherol traps mutagenic electrophiles such as NO\n                    <sub>x<\/sub>\n                    and complements \u03b1-tocopherol: Physiological\u2009implications"],"prefix":"10.1073","volume":"94","author":[{"given":"Stephan","family":"Christen","sequence":"first","affiliation":[{"name":"Division of Biochemistry and Molecular Biology, 401 Barker Hall, University of California, Berkeley, CA 94720; and School of Chemistry and Biomedical Mass Spectrometry Unit, University of New South Wales, Sydney NSW 2052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan A.","family":"Woodall","sequence":"additional","affiliation":[{"name":"Division of Biochemistry and Molecular Biology, 401 Barker Hall, University of California, Berkeley, CA 94720; and School of Chemistry and Biomedical Mass Spectrometry Unit, University of New South Wales, Sydney NSW 2052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark K.","family":"Shigenaga","sequence":"additional","affiliation":[{"name":"Division of Biochemistry and Molecular Biology, 401 Barker Hall, University of California, Berkeley, CA 94720; and School of Chemistry and Biomedical Mass Spectrometry Unit, University of New South Wales, Sydney NSW 2052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter T.","family":"Southwell-Keely","sequence":"additional","affiliation":[{"name":"Division of Biochemistry and Molecular Biology, 401 Barker Hall, University of California, Berkeley, CA 94720; and School of Chemistry and Biomedical Mass Spectrometry Unit, University of New South Wales, Sydney NSW 2052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark W.","family":"Duncan","sequence":"additional","affiliation":[{"name":"Division of Biochemistry and Molecular Biology, 401 Barker Hall, University of California, Berkeley, CA 94720; and School of Chemistry and Biomedical Mass Spectrometry Unit, University of New South Wales, Sydney NSW 2052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce N.","family":"Ames","sequence":"additional","affiliation":[{"name":"Division of Biochemistry and Molecular Biology, 401 Barker Hall, University of California, Berkeley, CA 94720; and School of Chemistry and Biomedical Mass Spectrometry Unit, University of New South Wales, Sydney NSW 2052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1997,4]]},"reference":[{"key":"e_1_3_3_1_2","volume-title":"Chronic Infection and Inflammation Lead to Mutation and Cancer","author":"Christen S","year":"1997","unstructured":"S Christen, T M Hagen, M K Shigenaga, B N Ames Chronic Infection and Inflammation Lead to Mutation and Cancer, eds J Parsonnet, S Horning (Oxford Univ. 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