Cytochrome P-455 nm complex formation in the metabolism of phenylalkylamines. VII. Enzyme interactions with synthetic 2-nitroso-1-phenylalkanes.
Cytochrome P-455 nm complex formation in rat liver microsomes was investigated with 2-nitroso-1-phenylpropane, the nitroso compound related to amphetamine, and six homologues comprising different alpha-alkyl substituents. The C-nitroso compounds were synthesized and obtained as trans nitroso dimers, the only form in which they are available in pure solid state. Their physical and chemical properties were investigated and their decomposition in ethanol solutions was correlated with the complexing efficacies of these solutions. Dissociation of the nitroso dimers to monomers constitutes an equilibrium which is displaced in favour of the dimer but with the monomers ultimately undergoing tautomerization to oximes. Based on these kinetics a mathematical model was produced, which by computer simulations gave simultaneously the dimer (Mo2), monomer (Mo) and oxime (Ox) concentrations of the substrate solutions used in the complex formation studies. The results show that the formation of cytochrome P-455 nm complexes is directly related to the numerically predicted concentrations of the nitroso monomers, but is very slow or absent when the dimer or oxime concentrations are at their highest. Substrate solutions derived from nitroso dimers with larger alpha-alkyl substituents (3-4 carbons) were devoid of complexing activities because of low solubility and very slow chemical kinetics.
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D003580:Cytochromes / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism; D009603:Nitroso Compounds / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D003580:Cytochromes; D009603:Nitroso Compounds; C039960:2-nitroso-1-phenylpropane; C029251:cytochrome P455