engleski

Slow Peroxidation of Low-Density Lipoprotein

Low-density lipoprotein (LDL) in solution, supplemented with EDTA, in the closed system, is spontaneously oxidized at physiological temperature. The oxidation is assumed to be initiated by the traces of the transition-metal ions associated with the lipoprotein. In the lag period no change of any of the usually measured oxidation markers have been detected. In the second phase oxygen is consumed and the level of hydroperoxides is increased. After consumption of oxygen, hydroperoxides decrease in concentration and the apoprotein-associated free radicals are formed. Concentration of oxygen was measured by EPR oximetry using the 3-carbamoyl-2,2,5,5-tetramethyl-3-pyroline-1-yloxy (CTPO). Free radicals were monitored for the samples supplemented before aging with spin trap N-t-butyl-alpha-phenylnitrone (PBN) with EPR. In the entire process alpha-tocopherol is conserved. The microscopic probabilistic model has been introduced to explain the kinetics of slow, tocopherol-mediated peroxidation of LDL. The substrates for the metal-ion attack are alpha-tocopherol and pre-formed lipid hydroperoxide. The theory assumes oscillation of the metal ions and alpha-tocopherol from the oxidized to the reduced states. The entire oxidation process consists of rare bursts of events in individual LDL particles. The reactions are treated in terms of probabilities of individual active species to participate in a specified reaction. The circular flow of the radical reactions colud be visualized as circular flow of microscopic probabilities. The empirical, macroscopic quantities are quantitatively related with the microscopic probabilities, determined by a set of adjustable parameters. The differential equations describing the rates of change of different oxidation markers are numerically solved in a finite difference approach. The calculated curves reproduce the observed features of slow LDL peroxidation. The kinetic model is applicable to other heterogeneous systems of compartmental structure.

EPR; LDL; oxidation

nije evidentirano