Human neutrophils employ myeloperoxidase to convert α-amino acids to a battery of reactive aldehydes: A pathway for aldehyde generation at sites of inflammation

Stanley L. Hazen, Fong F. Hsu, Andre D'Avignon, Jay W. Heinecke

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120 Scopus citations

Abstract

We have recently demonstrated that activated phagocytes employ the heme protein myeloperoxidase, H2O2, and Cl- to oxidize the aromatic amino acid L-tyrosine to the reactive aldehyde p-hydroxyphenylacetaldehyde. We now present evidence for the generality of this reaction by demonstrating that neutrophils employ the myeloperoxidase-H2O2-Cl- system to oxidize nearly all of the common α-amino acids to yield a family of reactive aldehydes. Chemical characterization suggested that reactive carbonyl moieties were generated during amino acid oxidation by myeloperoxidase. The structures of amino-acid-derived aldehydes were confirmed using a variety of mass spectrometric methods. Aldehyde production required myeloperoxidase, H2O2, Cl-, and an amino acid; it was inhibited by heme poisons and catalase. Hypochlorous acid was the apparent oxidizing intermediate because its addition to α-amino acids resulted in the formation of the anticipated aldehyde. Stimulated human neutrophils likewise generated aldehydes from all classes of α-amino acids by a pathway inhibited by heme poisons and catalase, implicating myeloperoxidase and H2O2 in the cell-mediated reaction. Aldehyde production accounted for a significant fraction of the H2O2 generated by stimulated neutrophils at physiological concentrations of amino acids. Collectively, these results suggest that amino-acid-derived aldehydes represent a product of reactive oxidant species generated by activated phagocytes.

Original languageEnglish
Pages (from-to)6864-6873
Number of pages10
JournalBiochemistry
Volume37
Issue number19
DOIs
StatePublished - May 12 1998

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