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

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.