A partition model for hepatic cytochrome P-450-hydrocarbon complex formation

Canady, WJ; Robinson, DA; Colby, HD

HERO ID

1483174

Reference Type

Journal Article

Year

1974

HERO ID 1483174
In Press No
Year 1974
Title A partition model for hepatic cytochrome P-450-hydrocarbon complex formation
Authors Canady, WJ; Robinson, DA; Colby, HD
Journal Biochemical Pharmacology
Volume 23
Issue 21
Page Numbers 3075-3078
Abstract HEEP COPYRIGHT: BIOL ABS. The significance of hydrophobicity in substrate binding to cytochrome P-450 was studied by examining hydrocarbon-induced spectral changes in rat hepatic microsomes. Benzene, ethylbenzene, toluene, xylene, indene and naphthalene produced typical type I difference spectra (increase in absorbancy at about 385 nm and a decrease at about 420 nm) upon addition to hepatic microsomal suspensions. The relative abilities of the aromatic hydrocarbons to bind to cytochrome P-450 were directly proportional to their tendencies to leave an aqueous solution and enter a hydrocarbon phase. Type I spectra were also produced by the non-aromatic compounds cyclohexene, n-hexane, and n-pentane (the association constant for each being 970, 830, and 371, respectively). Neither charge transfer complex formation nor a cyclic nor a flat molecule is essential for hydrocarbon-induced spectral changes. Binding of aromatic hydrocarbons is simply dependent upon molecular size. These results provide evidence that hydrophobic interaction is the greatest single factor in the binding of substrates to hepatic cytochrome P-450. Since hydrophobic interactions represent the sole mechanism for hydrocarbon-induced spectral changes in cytochrome P-450, these compounds will provide useful probes in further studies to evaluate the apparent hydrophobicity of cytochrome P-450 and/or its environment under various experimental conditions.
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Dupe Override 1483174
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