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

Chem Biol Interact. 1988;67(1-2):49-58. doi: 10.1016/0009-2797(88)90085-3.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytochrome P-450 Enzyme System / metabolism*
  • Cytochromes / metabolism*
  • Male
  • Microsomes, Liver / drug effects
  • Microsomes, Liver / enzymology*
  • NADP / metabolism
  • Nitroso Compounds / metabolism*
  • Phenobarbital / pharmacology
  • Rats
  • Rats, Inbred Strains
  • Stereoisomerism

Substances

  • Cytochromes
  • Nitroso Compounds
  • NADP
  • 2-nitroso-1-phenylpropane
  • cytochrome P455
  • Cytochrome P-450 Enzyme System
  • Phenobarbital