Human Phagocytes Employ the Myeloperoxidase-Hydrogen Peroxide System to Synthesize Dityrosine, Trityrosine, Pulcherosine, and Isodityrosine by a Tyrosyl Radical-dependent Pathway

摘要: Myeloperoxidase, a heme protein secreted by activated phagocytes, may be catalyst for lipoprotein oxidation in vivo. Active myeloperoxidase is component of human atherosclerotic lesions, and tissue exhibits selective enrichment dityrosine cross-links, well characterized product myeloperoxidase. Tyrosylation lipoproteins with peroxidase-generated tyrosyl radical generates multiple protein-bound tyrosine products addition to dityrosine. The structural characterization these would thus serve as an important step determining the role artery wall. We now report identification four distinct generated phagocytes. Activated neutrophils synthesized three major fluorescent from L-tyrosine; on reverse phase HPLC, each compound coeluted formed purified apparent homogeneity cation anion exchange chromatographies identified compounds (3,3′-dityrosine), trityrosine (3,3′,5′,3′-trityrosine) pulcherosine (5-[4′-(2-carboxy-2-aminoethyl)phenoxy]3,3′-dityrosine) high resolution NMR spectroscopy mass spectrometry. Additionally, we have found that precursor trityrosine, but not pulcherosine. In search pulcherosine, isodityrosine (3-[4′-(2-carboxy-2-aminoethyl)phenoxy]tyrosine), non-fluorescent L-tyrosine Our results represent first this family mammalian system. Moreover, markers specific radical-mediated oxidative damage atherosclerosis other inflammatory conditions.