Abstract

Recent work has suggested that the rate of hepatic microsomal drug metabolism may be correlated with either the cytochrome P-450 content or the magnitude of the spectral change caused by the addition of substrates to microsomal suspensions. Accordingly, the relationships between these factors were investigated in 0.9% NaCl- and phenobarbital-treated intact, sham-operated, and partially hepatectomized rats. In intact animals phenobarbital produced a 3-4-fold increase in both microsomal aniline hydroxylase activity and cytochrome P-450 content, whereas in sham-operated or partially hepatectomized rats it produced a 4-fold increase in cytochrome P-450 content but only doubled aniline hydroxylase activity. Although phenobarbital treatment doubled the binding constants (K_[unknown]) for aniline in all groups, it increased the maximum absorbance change (Amax) produced by the additione of aniline to microsomes about 7-fold in unoperated animals but only about 4-fold in the operated groups.

It was found that the Michaelis constant (K_m) and binding constant (K_[unknown]) for aniline differ by a factor of 10 in microsomal preparations from intact animals. Phenobarbital treatment was found to elicit significant increases in both K_[unknown], and K_m for aniline. These changes in K_m and K_[unknown], imply that induction by phenobarbital may be associated with qualitative as well as quantitative changes in the hepatic microsomal aniline hydroxylase.