The multiple effects of ethylenediaminetetraacetate in several model lipid peroxidation systems

Ming Tien, Lee A. Morehouse, John R. Bucher, Steven D. Aust

Research output: Contribution to journalArticle

86 Scopus citations

Abstract

Experiments were performed which illustrate the various ways EDTA can influence lipid peroxidation. Either detergent-dispersed linoleate, or liposomes made from extracted microsomal phospholipids were utilized as substrates for peroxidation. Peroxidation was accomplished using Fe2+ or Fe3+. In systems utilizing Fe2+, EDTA chelation facilitated Fe2+ autoxidation which in turn caused peroxidation of detergent-dispersed linoleate. Peroxidation was not initiated during EDTA-Fe2+ autoxidation when the substrate lipids were in a liposomal configuration. Systems utilizing Fe3+ required an enzyme (either xanthine oxidase or NADPH-cytochrome P450 reductase) to reduce the iron for peroxidative activity. EDTA chelation of Fe3+ enhanced the xanthine oxidase and NADPH-cytochrome P450 reductase-catalyzed peroxidation of detergent-dispersed linoleate, presumably by facilitating the reduction of Fe3+. Catalase and mannitol inhibited both EDTA-Fe2+- and EDTA-Fe3+-dependent lipid peroxidation. EDTA-Fe3+ was not capable of initiating peroxidation of phospholipid liposomes following enzymatic reduction by either enzyme, but ADP-chelated iron effectively initiated liposomal peroxidation in similar systems. With xanthine oxidase-catalyzed peroxidation of liposomes with ADP-Fe3+, the inclusion of EDTA-Fe3+ caused a modest enhancement of activity. EDTA-Fe3+ greatly stimulated NADPH-cytochrome P450 reductase-catalyzed peroxidation of liposomes with ADP-Fe3+. In contrast, the addition of EDTA, rather than EDTA-Fe3+ inhibited the liposomal peroxidation catalyzed by either enzyme with ADP-Fe3+ when the EDTA concentration exceeded the concentration of Fe3+.

Original languageEnglish (US)
Pages (from-to)450-458
Number of pages9
JournalArchives of Biochemistry and Biophysics
Volume218
Issue number2
DOIs
StatePublished - Oct 15 1982

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology

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