RT Journal Article SR Electronic T1 Source of the oxygen atom in the product of cytochrome P-450-catalyzed N-demethylation reactions. JF Molecular Pharmacology JO Mol Pharmacol FD American Society for Pharmacology and Experimental Therapeutics SP 758 OP 760 VO 23 IS 3 A1 G L Kedderis A1 L A Dwyer A1 D E Rickert A1 P F Hollenberg YR 1983 UL http://molpharm.aspetjournals.org/content/23/3/758.abstract AB The source of the oxygen atom in the product of the cytochrome P-450-catalyzed N-demethylation of N-methylcarbazole was determined by mass spectral analysis of the carbinolamine precursor of formaldehyde formed during incubation in oxygen 18-enriched medium. Initial experiments demonstrated that N-(hydroxymethyl)carbazole, the carbinolamine product of the metabolism of N-methylcarbazole, did not exchange oxygen with solvent water. When N-methylcarbazole was incubated in oxygen 18-enriched medium with purified cytochrome P-450 in the presence of either purified NADPH-cytochrome P-450 reductase and NADPH, cumene hydroperoxide, t-butyl hydroperoxide, or peracetic acid, there was no incorporation of oxygen 18 from the medium into N-(hydroxymethyl)carbazole. These results clearly demonstrate that the oxygen atom inserted into N-methylcarbazole by cytochrome P-450 to yield N-(hydroxymethyl)carbazole does not come from the medium and show that the N-demethylation reactions catalyzed by cytochrome P-450 proceed in a manner similar to hydroxylation reactions, with the oxygen atom in the product being derived from the oxidant.