The interaction of hepatic cytochrome P-450 with organic solvents. The effect of organic solvents on apparent spectral binding constants for hydrocarbon substrates.
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.
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
D012997:Solvents; D000431:Ethanol; D003577:Cytochrome P-450 Enzyme System; D006591:Hexobarbital; D008723:Methohexital