title: p-Hydroxyphenylacetaldehyde is the major product of L-tyrosine oxidation by activated human phagocytes. A chloride-dependent mechanism for the conversion of free amino acids into reactive aldehydes by myeloperoxidase.
abstract: Reactive aldehydes generated during lipid peroxidation have been implicated in the pathogenesis of atherosclerosis as well as other inflammatory diseases. A potential catalyst for such reactions is myeloperoxidase, a hemeprotein secreted by activated phagocytes. We now report that activated neutrophils utilize the myeloperoxidase-H2O2-chloride system to convert L-tyrosine to p-hydroxyphenylacetaldehyde. Production of p-hydroxyphenylacetaldehyde was nearly quantitative at physiological concentrations of L-tyrosine and chloride. Aldehyde generation required myeloperoxidase, H2O2, L-tyrosine, and chloride ion; it was inhibited by the H2O2 scavenger catalase and by the heme poisons azide and cyanide. Phorbol ester- and calcium ionophore-stimulated human neutrophils likewise generated p-hydroxyphenylacetaldehyde from L-tyrosine by a pathway inhibited by azide, cyanide, and catalase. Aldehyde production accounted for 75% of H2O2 generated by optimally stimulated neutrophils at plasma concentrations of L-tyrosine and chloride. Collectively, these results indicate that activated phagocytes, under physiological conditions, utilize myeloperoxidase to execute the chloride-dependent conversion of L-tyrosine to the lipid-soluble aldehyde, p-hydroxyphenylacetaldehyde, in near quantitative yield. Moreover, like aldehydes derived from lipid peroxidation, amino acid-derived aldehydes may exert potent biological effects in vascular lesions and other sites of inflammation.
authors.affiliation: Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
authors.forename: S L
authors.initials: SL
authors.lastname: Hazen
authors.forename: F F
authors.initials: FF
authors.lastname: Hsu
authors.forename: J W
authors.initials: JW
authors.lastname: Heinecke
mesh_terms: D000079:Acetaldehyde / Q000031:analogs & derivatives* / Q000378:metabolism*; D002478:Cells, Cultured; D002712:Chlorides / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D005583:Fourier Analysis; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D009504:Neutrophils / Q000378:metabolism*; D010084:Oxidation-Reduction; D009195:Peroxidase / Q000378:metabolism*; D010586:Phagocytes / Q000378:metabolism*; D019800:Phenol; D013481:Superoxides / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism*
chemical_list: D002712:Chlorides; D013481:Superoxides; D019800:Phenol; D014443:Tyrosine; C097891:4-hydroxyphenylacetaldehyde; C007543:dityrosine; D009195:Peroxidase; D000079:Acetaldehyde