Formation of hydrogen peroxide and N-hydroxylated amines catalyzed by pulmonary flavin-containing monooxygenases in the presence of primary alkylamines.
In atypical reaction, incubation of purified rabbit pulmonary flavin-containing monooxygenase with certain primary alkylamines results in the oxidation of NADPH and the formation of hydrogen peroxide. In addition, significant amounts of N-hydroxylated primary amine are also generated, as determined by colorimetric assay and GC/MS analysis of n-octylamine metabolites. Similar reactions appear to be catalyzed by the mouse pulmonary enzyme. In contrast, incubation of primary alkylamines with hepatic flavin-containing monooxygenases from rabbit, mouse, or pig does not result in NADPH oxidation or metabolism. Another effect of primary alkylamines is marked activation of the mouse pulmonary and pig hepatic flavin-containing monooxygenases with some substrates. The structural requirements for primary alkylamines to elicit NADPH oxidation by the rabbit pulmonary enzyme or to activate the mouse pulmonary and pig hepatic enzymes are identical. This indicates that different flavin-containing monooxygenases probably have a conserved alkylamine-binding site of defined specificity. In the case of the rabbit pulmonary enzyme, this binding may occur very close to or at the catalytic site resulting in some N-hydroxylation of the alkylamine.
D000588:Amines / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D002384:Catalysis; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006861:Hydrogen Peroxide / Q000096:biosynthesis*; D006900:Hydroxylation; D066298:In Vitro Techniques; D008099:Liver / Q000201:enzymology; D008168:Lung / Q000201:enzymology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009249:NADP / Q000378:metabolism; D010084:Oxidation-Reduction; D010105:Oxygenases / Q000378:metabolism*; D011817:Rabbits; D013045:Species Specificity; D013552:Swine
D000588:Amines; D009249:NADP; D006861:Hydrogen Peroxide; D010105:Oxygenases; C020066:dimethylaniline monooxygenase (N-oxide forming); C008699:octylamine