The second order mechanism of copper induced lipid peroxidation

In spite of the great interest and intensive research, the actual mechanism of copper-induced peroxidation is debatable. The accepted paradigm is that the two step mechanism (r.1,r.2) can be ruled out because reaction r.1 is "thermodynamically unfavorable", the redox potential of LO2· (range 0.77 V - 1.44 V) being higher than the redox potential of Cu(II) (0.16 V) LOOH + Cu2+= LO2· + H+ + Cu1+ r.1 LOOH + Cu1+= LO· + OH- + Cu2+ r.2 The sum of reactions r.1 and r.2 gives r.3 2LOOH=LO2·+ LO·+ H2O r.3 We think that the latter argument is not valid for systems far from equilibrium, particularly when the overall process (r.3) is thermodynamically favorable. Therefore the reaction may occur via the two steps mechanism. Alternatively, (i) additional reducing agents may reduce Cu(II) (ii) r.3 may involve intramolecular dismutation of an intermediate complex Cu(LOOH)x. The different mechanisms can be expected to result in different overall reaction orders. Experimentally, the dependence of peroxidation on the concentration of hydroperoxides accords with second order kinetics which is indicative for intermediate complex formation. This is also consistent with continuous peroxidation of lipids within any given lipoprotein particle only if the particle contains at least two hydroperoxide molecules. It also accords with the effects of deuteration of LDL on its peroxidation.