Myeloperoxidase-mediated oxidation of methionine and amino acid decarboxylation.
The myeloperoxidase (MPO)-mediated decarboxylation of amino acids and the MPO-mediated oxidation of methionine, two potential bactericidal mechanisms, were compared. In the presence of the MPO system (MPO, 50 mU/ml; H(2)O(2), 0.1 mM; Cl(-), 75 mM), 50% of alanine (0.1 mM) was decarboxylated, whereas only 5% of methionine (0.1 mM) was decarboxylated. In contrast, under similar conditions, 80% of methionine was oxidized to methionine sulfoxide. Once methionine was oxidized to methionine sulfoxide, it was decarboxylated (75%) by the MPO system. Methionine at 0.1 mM completely inhibited the decarboxylation of alanine, whereas alanine at a concentration 200 times that of methionine had no effect on the MPO-mediated oxidation of methionine. Sodium azide, an MPO inhibitor, inhibited the decarboxylation of alanine and the oxidation of methionine to the same extent. Tryptophan markedly inhibited the oxidation of methionine, whereas histidine stimulated it. Alanine, glycine, and taurine had no effect. In contrast, all of these amino acids and taurine markedly inhibited the MPO-mediated decarboxylation of alanine. NaN(3), tryptophan, and methionine, which inhibited the MPO-mediated oxidation of methionine, also inhibited the killing of Staphylococcus aureus or Klebsiella pneumoniae by the MPO system; whereas histidine, alanine, and glycine, which did not inhibit the oxidation of methionine, had less or no effect on the killing of these two bacteria by the MPO system. Results suggest that methionine is preferentially oxidized to methionine sulfoxide by the MPO system. Once methionine is oxidized to methionine sulfoxide, it is then readily decarboxylated by the MPO system. The agent responsible for the oxidation of methionine may play an important role in the MPO-mediated killing of bacteria.
D000409:Alanine / Q000378:metabolism*; D000596:Amino Acids / Q000494:pharmacology; D001386:Azides / Q000494:pharmacology; D003653:Decarboxylation; D007711:Klebsiella pneumoniae / Q000187:drug effects; D008715:Methionine / Q000031:analogs & derivatives / Q000378:metabolism*; D010084:Oxidation-Reduction; D009195:Peroxidase / Q000378:metabolism* / Q000494:pharmacology; D010544:Peroxidases / Q000378:metabolism*; D019810:Sodium Azide; D013211:Staphylococcus aureus / Q000187:drug effects; D013454:Sulfoxides / Q000378:metabolism
D000596:Amino Acids; D001386:Azides; D013454:Sulfoxides; D019810:Sodium Azide; D008715:Methionine; D010544:Peroxidases; D009195:Peroxidase; D000409:Alanine; C013111:methionine sulfoxide