The mechanism of the cytochrome P-448 mediated 6-hydroxylation of 7-ethoxycoumarin.
Deuterium labeling of 7-ethoxycoumarin on the carbon undergoing oxidation by cytochrome P-450 results in a redirection of metabolism from O-deethylation to ring hydroxylation at C6 (Harada, N. et al (1984) J Biol Chem 259, 3005-3010). Consequently, this substrate has been specifically labeled with deuterium at C6 aromatic in order to determine the mechanism of this ring hydroxylation reaction. Although product yield occurred over a 20-fold range when catalyzed by purified and microsomal preparations of cytochrome P-450, deuterium migration to C5 was always observed. Moreover, cumene hydroperoxide-supported reactions also proceeded with this NIH-shift. These data demonstrate that the 6-hydroxylation of 7-ethoxycoumarin occurs through a 5,6-oxide intermediate.
D015660:7-Alkoxycoumarin O-Dealkylase; D000818:Animals; D002384:Catalysis; D019388:Cytochrome P-450 CYP1A2; D003580:Cytochromes / Q000378:metabolism*; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008862:Microsomes, Liver / Q000201:enzymology; D010100:Oxygen / Q000032:analysis; D010105:Oxygenases / Q000378:metabolism*; D051381:Rats
D003580:Cytochromes; D010105:Oxygenases; D015660:7-Alkoxycoumarin O-Dealkylase; C017170:Cyp1a2 protein, rat; D019388:Cytochrome P-450 CYP1A2; D010100:Oxygen