Myeloperoxidase-dependent generation of a tyrosine peroxide by neutrophils.
It has recently been shown that tyrosyl radicals react with superoxide to form a peroxide adduct of tyrosine. Since myeloperoxidase oxidizes tyrosine to its radical, and neutrophils and monocytes contain myeloperoxidase as well as produce superoxide, we have investigated whether tyrosine peroxide could be a significant product of tyrosine oxidation by these cells. Oxidation of tyrosine by purified myeloperoxidase and a superoxide-generating system, and by stimulated human neutrophils, was found to generate peroxide adducts as detected in the xylenol orange (FOX) assay and by HPLC. Superoxide, hydrogen peroxide, and myeloperoxidase were required for formation of the peroxide. Dityrosine was also formed in each system, and in the presence of superoxide dismutase, suppression of tyrosine peroxide formation gave elevated formation of dityrosine. Quantitative estimates indicate that at physiological tyrosine concentration the peroxide is likely to be formed in preference to dityrosine and to be a significant product of neutrophils. This metastable peroxide therefore has the potential to contribute to neutrophil- or monocyte-mediated tissue injury.
Winterbourn
C C
CC
Department of Pathology, Christchurch School of Medicine, New Zealand. ccw@chmeds.ac.nz
Pichorner
H
H
Kettle
A J
AJ
D002851:Chromatography, High Pressure Liquid; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction; D009195:Peroxidase / Q000378:metabolism*; D010545:Peroxides / Q000302:isolation & purification / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000378:metabolism
D010545:Peroxides; C104002:tyrosine peroxide; D013481:Superoxides; D014443:Tyrosine; D006861:Hydrogen Peroxide; C007543:dityrosine; D009195:Peroxidase; D013755:Tetradecanoylphorbol Acetate