title: The interaction of hepatic cytochrome P-450 with organic solvents. The effect of organic solvents on apparent spectral binding constants for hydrocarbon substrates.
abstract: Studies have been undertaken to explain the observed variation of the apparent association constant for water-insoluble substrates, which were diluted in common organic solvents, as a direct function of the solvent/solute ratio. By the use of suitable equations, the solvents methanol, ethanol, propanol, and acetone are shown to interact with hydrocarbon substrates in a competitive manner in PB-treated male rats, with the solvent producing a type I spectral component. Such solvents are shown to elicit, in addition to the type I component, a modified type II component. In untreated rats, ethanol does not produce a type I component, and also does not affect the apparent association constant for the hydrocarbon substrates when used as a solvent for those substrates. All perturbations of the enzyme which cause a change in the apparent association constant of the substrate also cause a quantitatively similar change in the apparent association of the solvent for the enzyme. A sex difference, with respect to competitive solvent binding, is also observed. Cytochrome P-450 from untreated male rats is apparently unable to bind small polar solvent substrates at the hydrocarbon binding site, whereas untreated female rats possess such an ability. In PB-treated rats, solvent binding is found to be sex-dependent. With respect to PB induction in female rats, the binding affinity for ethanol in the PB-treated animals is significantly larger than that observed in untreated females.
mesh_terms: D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology; D005260:Female; D006591:Hexobarbital / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008433:Mathematics; D008723:Methohexital / Q000494:pharmacology; D008862:Microsomes, Liver / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D012997:Solvents / Q000494:pharmacology*; D013053:Spectrophotometry; D013329:Structure-Activity Relationship
chemical_list: D012997:Solvents; D000431:Ethanol; D003577:Cytochrome P-450 Enzyme System; D006591:Hexobarbital; D008723:Methohexital