Oxidative modification of low density lipoprotein (LDL) is thought to participate in the pathogenesis of atherosclerosis, but the pathways involved in such modification in vivo are poorly understood. The enzyme myeloperoxidase (MPO) is present in catalytically active form in human atherosclerotic lesions, and MPO can use a variety of substrates, including chloride, tyrosine, and nitrite, to generate oxidants that react with molecules in their environment. We have used mass spectrometry to identify and quantitate products of such reactions, including chlorinated cholesterol species, 3-chlorotyrosine, o-dityrosine, 3-nitrotyrosine, a family of reactive aldehydes derived from a-amino acids, and a lysine derivative formed by reaction with such aldehydes. We have developed isotope dilution GC/MS assays for such products that exploit the great sensitivity of negative ion electron capture MS analyses. These assays have permitted us to measure these products in cellular sys tems in vit ro and in LDL isolated from plasma and from human
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