Oxidation of N-hydroxynorzimeldine to a stable nitrone by hepatic monooxygenases.
Liver microsomes from uninduced hogs catalyzed the NADPH-dependent N-oxidation of the hydroxylamine (Z)-3-(4-bromophenyl)-N-hydroxy-N-methyl-3-(3-pyridyl)allylamine. The conjugated nitrone N-[(2Z)-3-(4-bromophenyl)-3-(3-pyridyl)-2-propenylidene]methylamin e N-oxide was the principal product and accounted for 90-95% of the total hydroxylamine metabolized by microsomes. The nitrone had a relatively high chemical stability which was investigated at various conditions. Studies of the biochemical mechanisms for N-oxidation of N-hydroxy-norzimeldine showed that the reaction was catalyzed by the flavin-containing monooxygenase. This conclusion was based on studies with the purified hog liver flavin-containing monooxygenase and hog liver microsomes. Purified rat liver cytochrome P-450IIB-1 was ineffective at catalyzing N-oxidation of N-hydroxynorzimeldine.
Cashman
J R
JR
Department of Pharmaceutical Chemistry, School of Pharmacy, University of California, San Francisco 94143.
Yang
Z C
ZC
Högberg
T
T
D000818:Animals; D006898:Hydroxylamines / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D009589:Nitrogen Oxides / Q000378:metabolism*; D010084:Oxidation-Reduction; D010105:Oxygenases / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013552:Swine; D015031:Zimeldine / Q000378:metabolism*
D006898:Hydroxylamines; D009589:Nitrogen Oxides; C015388:nitrones; D015031:Zimeldine; D010105:Oxygenases; C020066:dimethylaniline monooxygenase (N-oxide forming)