The effect of compartmentalization on the kinetics of transition metal ions-induced lipoprotein peroxidation

In a previous study, we proposed characterizing the typically observed kinetic profiles of transition metal ion-induced lipid peroxidation in terms of a limited number of characteristic time-points. These time-points can be derived from experimental time-dependencies and be presented in terms of rate constants and concentrations as calculated based on mechanistic considerations. The critical part of that analysis was that we had to assume that the experimental system behaves as if it is homogeneous, i.e., as if the reaction occurs in a solution. In spite of the uncertainties due to the latter assumption, we obtained a reasonable agreement between the experimental data and the theoretically predicted dependencies, which supports our theoretical treatment. Yet, several previous findings could not have been explained in terms of our ('quasi-homogeneous') model, indicating that the model is valid not under all conditions. One example is that under certain conditions, rapid peroxidation occurs prior to complete consumption of LDL-associated tocopherol. This can be attributed to compartmentalization of residual tocopherol, namely, after the onset of propagation, part of the LDL particles contain tocopherol, whereas in the other, tocopherol-depleted particles, the PUFA may undergo rapid LOOH-accelerated peroxidation only if they contain at least two hydroperoxides molecules per particle. In the present investigation, we show that the results of all our kinetic studies can be understood if we consider compartmentalization. Specifically, for any given composition of the particles (LDL and/or HDL), the kinetic results may be governed by the distribution and rate of exchange of antioxidants and hydroperoxides between particles. Our analysis is of special importance for systems containing more than one population of lipoprotein particles.