TY - JOUR
T1 - p-hydroxyphenylacetaldehyde is the major product of L-tyrosine oxidation by activated human phagocytes
T2 - A chloride-dependent mechanism for the conversion of free amino acids into reactive aldehydes by myeloperoxidase
AU - Hazen, Stanley L.
AU - Hsu, Fong Fu
AU - Heinecke, Jay W.
PY - 1996/1/26
Y1 - 1996/1/26
N2 - 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. * This work was supported in part by Grant RO1 AG12293 from the National Institutes of Health. Gas chromatography-mass spectrometry experiments were performed at the Washington University School of Medicine Mass Spectrometry Resource (supported by National Institutes of Health Grant RR00954). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
AB - 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. * This work was supported in part by Grant RO1 AG12293 from the National Institutes of Health. Gas chromatography-mass spectrometry experiments were performed at the Washington University School of Medicine Mass Spectrometry Resource (supported by National Institutes of Health Grant RR00954). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
UR - http://www.scopus.com/inward/record.url?scp=0030053876&partnerID=8YFLogxK
U2 - 10.1074/jbc.271.4.1861
DO - 10.1074/jbc.271.4.1861
M3 - Article
C2 - 8567631
AN - SCOPUS:0030053876
SN - 0021-9258
VL - 271
SP - 1861
EP - 1867
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 4
ER -