Prostaglandin H synthase-catalyzed ring oxygenation of 2-naphthylamine: evidence for two distinct oxidation pathways.
Previous studies showed that prostaglandin H synthase (PHS) cooxidizes 2-naphthylamine (2-NA) to ring-oxygenated products. These metabolites are atypical for a peroxidase-mediated reaction and are completely different from the polymeric nonoxygenated metabolites of 2-NA that are generated with the model peroxidase horseradish peroxidase (HRP). In this study, we investigated possible explanations for the PHS-catalyzed formation of ring-oxygenated 2-NA metabolites. We found that introduction of a peroxyl radical-generated cosubstrate into the HRP/2-NA system resulted in the formation of the same ring-oxygenated products observed in the PHS/2-NA system. 18O2 incorporation studies were utilized to further characterize the source of oxygen in the ring-oxygenated 2-NA metabolites. The data show that, in the case of PHS, ring oxygenation can occur both by peroxyl radical-mediated attack on 2-NA and by direct transfer of peroxide oxygen from PHS to 2-NA.
D015081:2-Naphthylamine / Q000378:metabolism*; D000818:Animals; D002273:Carcinogens / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D006735:Horseradish Peroxidase / Q000737:chemistry; D008297:Male; D013058:Mass Spectrometry; D008956:Models, Chemical; D010084:Oxidation-Reduction; D010100:Oxygen / Q000737:chemistry*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D012756:Sheep; D013056:Spectrophotometry, Ultraviolet
D002273:Carcinogens; D015081:2-Naphthylamine; D006735:Horseradish Peroxidase; D011451:Prostaglandin-Endoperoxide Synthases; D010100:Oxygen