Fluidity of the microsomal membrane and cytochrome P450 reduction kinetics of pig liver microsomes as a consequence of organic solvent impact

Xenobiotica. 1993 Jan;23(1):71-8. doi: 10.3109/00498259309059363.

Abstract

1. The effect of the aromatic solvents toluene, xylene and ethylbenzene on microsomal membrane fluidity and anaerobic NADPH-reduction kinetics were studied. 2. The relation of membrane fluidity to the kinetics of cytochrome P450 reduction by NADPH-cytochrome P450 reductase was examined with regard to a membrane-mediated molecular organization of the multienzyme components of the monooxygenase system. 3. Membrane fluidity changes were detected with the steady-state pyrene excimer formation method and with fluorescence lifetime measurements after incubation of the microsomes with organic solvents. 4. Increase in membrane fluidity in presence of organic solvents leads to a small but significant decrease of the rate constant of the cytochrome P450 reduction kinetics and a change in the relative amplitudes of the components of the biphasic response. 5. The results support the idea of a molecular organization of cytochrome P450 in clusters. Fluidization of the microsomal membrane by organic solvents increase the cytochrome P450 cluster formation.

MeSH terms

  • Animals
  • Benzene Derivatives / pharmacology*
  • Cytochrome P-450 Enzyme System / drug effects*
  • Cytochrome P-450 Enzyme System / metabolism
  • Intracellular Membranes / drug effects*
  • Intracellular Membranes / enzymology*
  • Kinetics
  • Membrane Fluidity / drug effects*
  • Microsomes, Liver / drug effects*
  • Microsomes, Liver / enzymology*
  • Solvents / pharmacology*
  • Swine

Substances

  • Benzene Derivatives
  • Solvents
  • Cytochrome P-450 Enzyme System