Oxidation of vitamin E during iron-catalyzed lipid peroxidation: evidence for electron-transfer reactions of the tocopheroxyl radical.
Incubation of phosphatidylcholine liposomes containing the biological antioxidant alpha-tocopherol (alpha-TH) with xanthine, xanthine oxidase, and FeCl2 caused alpha-TH oxidation to alpha-tocopherol quinone (alpha-TQ) and 8a-hydroperoxytocopherone (2). In addition, 4a,5-epoxy-8a-hydroperoxytocopherone (3), 7,8-epoxy-8a-hydroperoxytocopherone (4), and their respective hydrolysis products 2,3-epoxy-alpha-tocopherol quinone (6) and 5,6-epoxy-alpha-tocopherol quinone (7) also were formed. alpha-TQ was the major product at less than 20% alpha-TH oxidation, whereas epoxides were the predominant products when alpha-TH was more extensively oxidized. 8a-(Alkyldioxy)tocopherones 1, which are formed when peroxyl radicals oxidize alpha-TH in other systems and which are precursors to alpha-TQ, were not found. 8a-Hydroxytocopherone (5), rather than 8a-(alkyldioxy)tocopherones 1, appeared to be the precursor to alpha-TQ. Approximately 30% of the alpha-TH consumed was regenerated by treatment of samples with ascorbic acid or nordehydroguaiaretic acid (NDGA) at pH 3, but not at pH 7. The stability of the ascorbic acid- and NDGA-reducible species and pH dependence for regeneration matched those of 8a-hydroxytocopherone (5) and contrasted with the properties of the tocopheroxyl radical (alpha-T.). Incubation of liposomes containing alpha-TH with the diphenylpicrylhydrazyl (DPPH) radical, which oxidizes alpha-TH to alpha-T. in high yield, formed an ascorbic acid-reducible species with properties identical to those of compound 5. The results indicate that phospholipid peroxyl radicals oxidize alpha-T. to epoxides, 8a-hydroperoxytocopherone (2), and the tocopherone cation (alpha-T+), which hydrolyzes to 5, the immediate precursor to alpha-TQ.(ABSTRACT TRUNCATED AT 250 WORDS)
Liebler
D C
DC
Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson 85721.
Burr
J A
JA
D001205:Ascorbic Acid; D002851:Chromatography, High Pressure Liquid; D004579:Electron Transport; D005609:Free Radicals / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007501:Iron; D007700:Kinetics; D015227:Lipid Peroxidation; D008081:Liposomes; D015394:Molecular Structure; D010084:Oxidation-Reduction; D010713:Phosphatidylcholines; D013481:Superoxides; D014810:Vitamin E / Q000737:chemistry*
D005609:Free Radicals; D008081:Liposomes; D010713:Phosphatidylcholines; D013481:Superoxides; C066323:tocopheroxy radical; D014810:Vitamin E; D007501:Iron; D001205:Ascorbic Acid