Human neutrophils employ myeloperoxidase to convert alpha-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 alpha-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 alpha-amino acids resulted in the formation of the anticipated aldehyde. Stimulated human neutrophils likewise generated aldehydes from all classes of alpha-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.
Hazen
S L
SL
Department of Medicine, Washington University, St. Louis, MO 63110, USA.
Hsu
F F
FF
d'Avignon
A
A
Heinecke
J W
JW
D000447:Aldehydes / Q000097:blood*; D000596:Amino Acids / Q000097:blood*; D002384:Catalysis; D002712:Chlorides / Q000097:blood; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D006861:Hydrogen Peroxide / Q000097:blood; D006997:Hypochlorous Acid / Q000097:blood; D007249:Inflammation / Q000097:blood; D018375:Neutrophil Activation; D009504:Neutrophils / Q000201:enzymology* / Q000473:pathology; D010084:Oxidation-Reduction; D009195:Peroxidase / Q000097:blood*
D000447:Aldehydes; D000596:Amino Acids; D002712:Chlorides; D006997:Hypochlorous Acid; D006861:Hydrogen Peroxide; D009195:Peroxidase