Cytochrome P-455 nm complex formation in the metabolism of phenylalkylamines. IX. A comparative study with enantiomeric 2-nitroso-1-phenylpropane in microsomes and a reconstituted cytochrome P-450 system from rat liver.
Formation of cytochrome P-455 nm complexes was investigated with enantiomeric 2-nitroso-1-phenylpropane--the C-nitroso analogue of amphetamine--and optically active N-hydroxyamphetamine, in the presence of NADPH. For comparative reasons, three different drug-metabolizing enzyme systems were used, namely microsomes from control and phenobarbital-treated rats, and a reconstituted system containing the main phenobarbital-induced form of cytochrome P-450 from rat liver. In microsomes obtained from phenobarbital-treated rats, pronounced differences in the kinetics of complex formation were observed between the enantiomeric C-nitroso compounds, but not between the isomers of N-hydroxyamphetamine. In the reconstituted enzyme system the S-nitroso compound formed the P-455 nm chromophore at the highest initial rate, while the R analogue was devoid of complexing activity. The rates of complex formation from the N-hydroxylamine enantiomers were high and equal.
Paulsen-Sörman
U
U
Pharmacia-Leo Pharmaceutical AB, Uppsala, Sweden.
Jönsson
K H
KH
Lindeke
B
B
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D003580:Cytochromes / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D009249:NADP / Q000378:metabolism; D009603:Nitroso Compounds / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013237:Stereoisomerism
D003580:Cytochromes; D009603:Nitroso Compounds; D009249:NADP; C039960:2-nitroso-1-phenylpropane; C029251:cytochrome P455; D003577:Cytochrome P-450 Enzyme System; D010634:Phenobarbital