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15. The Oxidation of Linoleic Acid by Copper(II) Complexes
Jun-ichi Ueda and Toshihiko Ozawa
Keywords: linoleic acid, copper(II) complexes, lipid peroxidation, HPLC
The oxidation of lipid by active oxygen species or metal ions has been hypothesized to play a critical role in diverse biological processes including carcinogenesis and radiation damage. Then, we intended to investigate how linoleic acid, one of the main constituents of lipid in membrane, is oxidized by metal ions such as Cu(II) complexes. The following Cu(II) complexes were used: Cu(BC)2 (BC: bathocuproine ); Cu(CyHH)2 (CyHH: cyclo(L-histidylhistidyl)); Cu(OP)2 (OP: o-phenanthroline); Cu(HGG) (HGG: L-histidylglycylglycine): and Cu(en)2 (en: ethylenediamine).
Lipid peroxidation proceeds through a chain reaction initiated by the abstraction of a hydrogen atom from polyunsaturated fatty acids containing unconjugated 1,4-dienes to yield conjugated dienes with a characteristic UV absorption around 234 nm. The absorbance at 234 nm observed during Cu(II)-catalyzed oxidation of linoleic acid increased with incubation time, reached a maximum level, and decreased thereafter. HPLC chromatograms due to oxidation products indicated the appearance of peaks corresponding to four isomers of linoleic acid hydroperoxide (LOOH) and subsequent complete decomposition of LOOH. The time to reach the maximum absorbance at 234 nm within 24 h was in the following order: Cu(II)(BC)2 > Cu(II)(CyHH)2 = Cu(II)(OP)2 > Cu(II)(en)2 > Cu(II)(HGG). This result suggests that Cu(II)(BC)2 can produce LOOH from linoleic acid more rapidly than Cu(II)(HGG) and it can decompose the LOOH generated more easily. Also lipid peroxidation, i.e. the formation of lipid hydroperoxide, may depend on the redox potential of Cu(II) complexes, since that of Cu(II)(BC)2 of 620 mV (versus NHE) is the highest among the five Cu(II) complexes and the redox potentials of the other four Cu(II) complexes have the following order: Cu(II)(CyHH)2 > Cu(II)(OP)2 > Cu(II)(HGG) > Cu(II)(en)2. It has been reported that the change in redox potential of copper markedly influenced the rate of oxidation of lipids induced by copper.
Further, whether the decomposition of LOOH was caused by these Cu(II) complexes was investigated. The absorbance at 234 nm due to LOOH, which was separately synthesized from the reaction of linoleic acid with soybean lipoxygenase, decreased rapidly with incubation time in the presence of Cu(II) complexes. HPLC also indicated the disappearance of LOOH and the appearance of unidentified degradation products.
These results suggest that Cu(II) complexes can not only oxidize linoleic acid, but also decompose LOOH generated from it.
