The Cu(II)-promoted oxidation of lipids is a lipid hydroperoxide (LOOH)-dependent process that has been used routinely to assess the oxidizability of low-density lipoprotein (LDL) in human subjects. Metal-dependent redox reactions, including those mediated by copper, have been implicated in the pathogenesis of atherosclerosis. Despite its widespread use and possible biological significance, key elements of the mechanism are not clear. For example, although it is evident that copper acts as a catalyst, which implies a redox cycle between the Cu(II) and Cu(I) redox states, the reductants remain uncertain. In LDL these could include α-tocopherol, amino acid residues on the protein and LOOH. However, both α-tocopherol and amino acid residues are probably consumed before the most rapid phase of lipid peroxidation occurs, suggesting that another reductant must be donating electrons to Cu(II), the most likely candidate being LOOH. This role has been disputed, since LDLs nominally devoid of LOOH are still capable of reducing Cu(II) to Cu(I) and thermodynamic calculations for this reaction are not favourable. Direct investigation of the role of LOOH as reductant has not been reported and in the present study, using simple lipid systems and LDL, we have re-examined this issue using the Cu(I) chelator bathocuproine. We have shown that Cu(II) may promote lipid peroxidation in liposomes, which do not contain either protein or α-tocopherol, and that this is associated with reduction to Cu(I). The data also indicate that an equilibrium between free Cu(II) and LOOH exists, which only in the presence of an oxidizable substrate, i.e. unsaturated fatty acids, is shifted towards formation of Cu(I) and lipid-derived peroxyl radicals. We propose that reduction of Cu(II) by LOOH is a necessary component in sustaining the propagation of lipid peroxidation and that the formation of peroxyl radicals and their products in a lipid environment is sufficient to overcome thermodynamic barriers to the reaction.
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March 1997
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Research Article|
March 01 1997
Reduction of Cu(II) by lipid hydroperoxides: implications for the copper-dependent oxidation of low-density lipoprotein
Rakesh P. PATEL;
Rakesh P. PATEL
*Department of Biological and Chemical Sciences (Central Campus), University of Essex, Colchester, Essex CO4 3SQ, U.K.
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Dimitri SVISTUNENKO;
Dimitri SVISTUNENKO
*Department of Biological and Chemical Sciences (Central Campus), University of Essex, Colchester, Essex CO4 3SQ, U.K.
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Michael T. WILSON;
Michael T. WILSON
*Department of Biological and Chemical Sciences (Central Campus), University of Essex, Colchester, Essex CO4 3SQ, U.K.
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Victor M. DARLEY-USMAR
Victor M. DARLEY-USMAR
‡
†Center for Free Radical Biology, Department of Pathology, Molecular and Cellular Division, University of Alabama at Birmingham, Volker Hall Room GO38, 1670 University Boulevard, Birmingham, AL 35294-0019, U.S.A.
†To whom correspondence should be addressed.
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Biochem J (1997) 322 (2): 425–433.
Article history
Received:
August 14 1996
Revision Received:
October 16 1996
Accepted:
October 21 1996
Citation
Rakesh P. PATEL, Dimitri SVISTUNENKO, Michael T. WILSON, Victor M. DARLEY-USMAR; Reduction of Cu(II) by lipid hydroperoxides: implications for the copper-dependent oxidation of low-density lipoprotein. Biochem J 1 March 1997; 322 (2): 425–433. doi: https://doi.org/10.1042/bj3220425
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