Dityrosine, a specific marker of oxidation, is synthesized by the myeloperoxidase-hydrogen peroxide system of human neutrophils and macrophages

Myeloperoxidase, secreted by activated phagocytes, produces the powerful cytotoxin hypochlorous acid from H2O2 and Cl-. We show that the enzyme can also employ H2O2 to oxidize L-tyrosine to tyrosyl radical, yielding the stable cross-linked product dityrosine. Dityrosine synthesis by the myeloperoxid...

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Published in:	The Journal of biological chemistry Vol. 268; no. 6; pp. 4069 - 4077
Main Authors:	J W Heinecke, W Li, H L Daehnke, 3rd, J A Goldstein
Format:	Journal Article
Language:	English
Published:	Bethesda, MD American Society for Biochemistry and Molecular Biology 25-02-1993
Subjects:	Aminoacids, peptides. Hormones. Neuropeptides Analytical, structural and metabolic biochemistry Biological and medical sciences Cells, Cultured Chromatography, Liquid Free Radicals Fundamental and applied biological sciences. Psychology Humans Hydrogen Peroxide - metabolism Hydrogen-Ion Concentration Kinetics Macrophages - enzymology Macrophages - metabolism Mass Spectrometry Neutrophils - enzymology Neutrophils - metabolism Oxidation-Reduction Peroxidase - metabolism Proteins Spectrum Analysis Tyrosine - analogs & derivatives Tyrosine - biosynthesis Tyrosine - metabolism Human Tyrosine Regulation(control) Enzyme Biological marker Peroxidase Neutrophil Dimerization Macrophage
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Summary:	Myeloperoxidase, secreted by activated phagocytes, produces the powerful cytotoxin hypochlorous acid from H2O2 and Cl-. We show that the enzyme can also employ H2O2 to oxidize L-tyrosine to tyrosyl radical, yielding the stable cross-linked product dityrosine. Dityrosine synthesis by the myeloperoxidase-H2O2 system did not require halide and was partially inhibited by Cl-. At physiological concentrations of Cl-, L-tyrosine, and other plasma amino acids, purified myeloperoxidase utilized 26% of the H2O2 in the reaction mixture to form dityrosine. Aminotriazole, cyanide, and azide inhibited the reaction. Phorbol ester-stimulated human neutrophils and monocyte-derived macrophages similarly generated dityrosine from L-tyrosine by a pathway inhibited by catalase, aminotriazole, and azide. The requirement for H2O2 and the inhibition by heme poisons suggest that activated phagocytes synthesize dityrosine by a peroxidative mechanism. These results indicate that L-tyrosine can compete effectively with Cl- as a substrate for myeloperoxidase and raise the possibility that formation of tyrosyl radical may play a role in the phagocyte inflammatory response. Because dityrosine is protease-resistant, stable to acid hydrolysis, and intensely fluorescent, its identification in tissues may pinpoint targets where phagocytes inflict oxidative damage in vivo.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23
ISSN:	0021-9258 1083-351X
DOI:	10.1016/s0021-9258(18)53581-x