P-HYDROXYPHENYLACETALDEHYDE IS THE MAJOR PRODUCT OF L-TYROSINE OXIDATION BY ACTIVATED HUMAN PHAGOCYTES - A CHLORIDE-DEPENDENT MECHANISM FORTHE CONVERSION OF FREE AMINO-ACIDS INTO REACTIVE ALDEHYDES BY MYELOPEROXIDASE

Reactive aldehydes generated during lipid peroxidation have been impli cated in the pathogenesis of atherosclerosis as well as other inflamma tory diseases, A potential catalyst for such reactions is myeloperoxid ase, a hemeprotein secreted by activated phagocytes. We now report tha t activated neutrophils utilize the myeloperoxidase-H2O2-chloride syst em to convert L-tyrosine to p-hydroxyphenylacetaldehyde. Production of p-hydroxyphenylacetaldehyde was nearly quantitative at physiological concentrations of L-tyrosine and chloride, Aldehyde generation require d myeloperoxidase, H2O2, L-tyrosine, and chloride ion; it was inhibite d by the H2O2 scavenger catalase and by the heme poisons azide and cya nide. Phorbol ester- and calcium ionophore-stimulated human neutrophil s 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 neutrophi ls 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-hydroxypheny lacetaldehyde, in near quantitative yield, Moreover, like aldehydes de rived from lipid peroxidation, amino acid-derived aldehydes may exert potent biological effects in vascular lesions and other sites of infla mmation.