title: A comparison of the kinetics of low-density lipoprotein oxidation initiated by copper or by azobis (2-amidinopropane).
abstract: This article describes the kinetics of low density lipoprotein (LDL) oxidation catalyzed by azobis (2-amidinopropane) dihydrochloride, ABAP, or by copper. The LDLs were isolated from nonhuman primates fed diets enriched in one of three types of fatty acids: saturated fatty acids, monounsaturated fatty acids, predominantly, oleic acid, or polyunsaturated fatty acids, predominantly linoleic acid. Oxidation was followed by monitoring the formation of conjugated diene hydroperoxides from polyunsaturated fatty acids (PUFA). For both copper and ABAP-initiated oxidation, the rate of LDL oxidation depended on the concentrations of initiator, PUFA, and LDL. Except for the dependence on PUFA concentration the rate of LDL oxidation was not directly influenced by the fatty acid composition of the LDL particle. The two initiators had very different dependence on initiator concentration. Because LDL particles are essentially small, lipid-rich droplets, the kinetic descriptions of LDL oxidation assumed: (1), that there was only one chain per particle, and (2) that the radical chain was terminated when a second radical either entered or was formed in the particle. When two LDL samples having very different lag times were mixed, the oxidation profile was bimodal. This finding demonstrated that the oxidation of native LDL particles was independent of the oxidation state of the other native LDL particles in solution, i.e., LDL particles do not rapidly exchange radicals, for example, hydroperoxyl radicals. Oxidation initiated by ABAP was proportional to [ABAP]0.5, suggesting that hydroperoxyl radical recombination between the lipid hydroperoxyl radical and the ABAP-hydroperoxyl radical was the chain-terminating step. The reciprocal of the rate of copper oxidation was linearly related to the reciprocal copper concentration, demonstrating that the binding of copper to LDL was necessary to initiate oxidation. This binding constant showed considerable variability among LDL samples. The kinetic descriptions of LDL oxidation reflect the differences in the mechanisms of initiation and termination.
authors.affiliation: Department of Biochemistry, Wake Forest University Medical Center, Winston-Salem, NC 27157, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Thomas
authors.forename: Q
authors.initials: Q
authors.lastname: Chen
authors.forename: C
authors.initials: C
authors.lastname: Franklin
authors.forename: L L
authors.initials: LL
authors.lastname: Rudel
mesh_terms: D000578:Amidines / Q000097:blood / Q000378:metabolism*; D000818:Animals; D002384:Catalysis; D002522:Chlorocebus aethiops; D003300:Copper / Q000097:blood / Q000378:metabolism*; D005609:Free Radicals / Q000097:blood / Q000378:metabolism; D007700:Kinetics; D008077:Lipoproteins, LDL / Q000097:blood / Q000378:metabolism*; D008252:Macaca fascicularis; D010084:Oxidation-Reduction; D010545:Peroxides / Q000097:blood / Q000378:metabolism
chemical_list: D000578:Amidines; D005609:Free Radicals; D008077:Lipoproteins, LDL; D010545:Peroxides; C099252:oxidized low density lipoprotein; C046728:2,2'-azobis(2-amidinopropane); D003300:Copper