Kinetic analysis of copper-induced peroxidation of LDL

We have employed our recently developed spectroscopic method of continuous monitoring of lipid oxidation to study the formation and decomposition of hydroperoxides in the time course of LDL oxidation. The results show satisfactory agreement with simulated time courses based on the following assumptions: (a) Both the rates of formation and decomposition of hydroperoxides depend on the ratio of bound copper to LDL as computed under the assumption that each LDL particle has 17 equivalent copper binding sites characterized by a dissociation constant K = 1 mu M. (b) Peroxidation is initiated by copper-catalyzed decomposition of hydroperoxides (LOOH) into peroxy radicals (LOO) and other products, including dienals. Under these assumptions, the rate of accumulation of LOOH can be computed from the equation dLOOH/dt = k(f) . LOOH . LH-k(d) . LOOH2, where k(f) and k(d) are the following functions of the copper-independent rate constants of initiation (k(i)), propagation (k(p)) and termination (k(t)) k(f) = k(p).root k(i) . Cu-B/2k(t) and k(d) = k(i) . Cu-B. The agreement between the simulated and experimentally-observed kinetics supports the assumptions used for simulations. The close agreement between the values of lipid oxidizability (k(p)/root 2k(t)) obtained for LDL (0.035 (Ms)(-1/2)) and previously published data on the oxidizability of linoleates (0.02-0.11 (Ms)(-1/2)) lends further support for these assumptions. (C) 1998 Elsevier Science B.V.