PROSTAGLANDIN-H SYNTHASE-CATALYZED RING OXYGENATION OF 2-NAPHTHYLAMINE - EVIDENCE FOR 2 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 di fferent from the polymeric nonoxygenated metabolites of 2-NA that are generated with the model peroxidase horseradish peroxidase (HRP). In t his study, we investigated possible explanations for the PHS-catalyzed formation of ring-oxygenated 2-NA metabolites. We found that introduc tion of a peroxyl radical-generated cosubstrate into the HRP/2-NA syst em resulted in the formation of the same ring-oxygenated products obse rved in the PHS/2-NA system. O-18(2) incorporation studies were utiliz ed to further characterize the source of oxygen in the ring-oxygenated 2-NA metabolites. The data show that, in the ease of PHS, ring oxygen ation can occur both by peroxyl radical-mediated attack on 2-NA and by direct transfer of peroxide oxygen from PHS to 2-NA.