An investigation into the mechanism of citrate-Fe2+-dependent lipid peroxidation.
Chelation by citrate was found to promote the autoxidation of Fe2+, measured as the disappearance of 1,10-phenanthroline-chelatable Fe2+. The autoxidation of citrate-Fe2+ could in turn promote the peroxidation of microsomal phospholipid liposomes, as judged by malondialdehyde formation. At low citrate-Fe2+ ratios the autoxidation of Fe2+ was slow and the formation of malondialdehyde was preceded by a lag phase. The lag phase was eliminated by increasing the citrate-Fe2+ ratio, which also increased the rate of Fe2+ autoxidation. The Fe2+ autoxidation product required for the initiation of lipid peroxidation was characterized as being Fe3+. As direct evidence of this, linear initial rates of lipid peroxidation were obtained via the combination of citrate-Fe2+ and citrate-Fe3+, optimum activity occurring at a Fe3+-Fe2+ ratio of 1:1. Evidence is also presented to suggest that the superoxide and the hydrogen peroxide that are formed during the autoxidation of citrate-Fe2+ can either stimulate or inhibit lipid peroxidation by affecting the yield of citrate-Fe3+ from citrate-Fe2+. No evidence was obtained for the participation of the hydroxyl radical in the initiation of lipid peroxidation by citrate-Fe2+.
D000818:Animals; D002374:Catalase / Q000494:pharmacology; D002951:Citrates / Q000378:metabolism*; D005296:Ferrous Compounds / Q000378:metabolism; D066298:In Vitro Techniques; D007501:Iron / Q000378:metabolism*; D050356:Lipid Metabolism; D008054:Lipid Peroxides / Q000378:metabolism*; D008081:Liposomes / Q000378:metabolism; D008297:Male; D008353:Mannitol / Q000494:pharmacology; D008862:Microsomes, Liver / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains; D013482:Superoxide Dismutase / Q000494:pharmacology; D014969:Xanthine Oxidase / Q000494:pharmacology
D002951:Citrates; D005296:Ferrous Compounds; D008054:Lipid Peroxides; D008081:Liposomes; D008353:Mannitol; D007501:Iron; D002374:Catalase; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase