title: Comparison of aniline hydroxylation by hemoglobin and microsomal cytochrome P450 using stable isotopes.
abstract: Hemoglobin (Hb) and cytochrome P450 carry out aromatic ring hydroxylation of aniline. In the presence of reductants and Hb, para- and ortho-aminophenol were formed. Under [18O]O2, 100% of product was labeled; no incorporation occurred with [18O]H2O. Deuterium (1.9%) was detectable in p-aminophenol formed from p-[2H]aniline by Hb, as compared with 6% retention observed with cytochrome P450. These observations are consistent with a mechanism for Hb-dependent reaction involving formation of an iron-oxo complex competent to hydroxylate substrate. Hb-mediated reactions may represent a source of extrahepatic metabolism since Hb is a major carrier for small organic molecules. The similarities of P450- and Hb-mediated aniline hydroxylation using stable isotopes preclude their use as in vivo probes.
authors.affiliation: Program in Toxicology, Massachusetts Institute of Technology, Cambridge.
authors.forename: H A
authors.initials: HA
authors.lastname: Barton
authors.forename: M A
authors.initials: MA
authors.lastname: Marletta
mesh_terms: D000814:Aniline Compounds / Q000378:metabolism*; D000818:Animals; D002384:Catalysis; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D006900:Hydroxylation; D007554:Isotopes; D008862:Microsomes, Liver / Q000201:enzymology; D051381:Rats
chemical_list: D000814:Aniline Compounds; D006454:Hemoglobins; D007554:Isotopes; D003577:Cytochrome P-450 Enzyme System; C023650:aniline