Paradoxical actions of antioxidants in the oxidation of low density lipoprotein by peroxidases.
Oxidation of LDL by peroxidases has been suggested to be a model for in vivo oxidation. The mechanism might involve the generation of an intermediate radical such as a phenoxy radical. We show that, in contrast to the oxidation of LDL by copper, oxidation by peroxidase system (H2O2/horse radish peroxidase) showed less resistance. This suggested that either the antioxidants were consumed more rapidly or might have actually participated in the oxidation. Accordingly, addition of vitamin E increased the rate of oxidation of LDL. In contrast, probucol inhibited the oxidation even at low concentrations suggesting ineffective formation of probucol radical or the sterically hindered probucol radical was inefficient in catalyzing subsequent oxidation. The oxidation of LDL by horse radish peroxidase was also enhanced in the presence of diphenylphenylenediamine, an antioxidant that does not have a phenolic -OH group. Myeloperoxidase was able to oxidize LDL even in the absence of added tyrosine suggesting that it was able to utilize the LDL-associated vitamin E. Addition of free tyrosine inhibited the formation of conjugated dienes. We suggest that if peroxidases are involved in the initiation of LDL oxidation in vivo, higher concentrations of antioxidants may be indicated to inhibit propagation of oxidation.
Santanam
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N
Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Parthasarathy
S
S
D000975:Antioxidants / Q000737:chemistry*; D006801:Humans; D066298:In Vitro Techniques; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000737:chemistry; D008077:Lipoproteins, LDL / Q000737:chemistry*; D008958:Models, Molecular; D010544:Peroxidases / Q000378:metabolism*; D011341:Probucol / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014443:Tyrosine / Q000737:chemistry; D014810:Vitamin E / Q000737:chemistry
D000975:Antioxidants; D008041:Linoleic Acids; D008077:Lipoproteins, LDL; D014810:Vitamin E; D014443:Tyrosine; D019787:Linoleic Acid; D010544:Peroxidases; D011341:Probucol