| Abstract: | The main nongenetic factors are revealed which regulate the catalytic activity and substrate specificity of microsomal monooxygenases preinduced by phenobarbital-type xenobiotics (barbituric acid and pyrazolone derivatives). It is shown that a blockage of the primary microsomal metabolism of an inducer is the obligate condition for its inductive effect on the content and activity of cytochrome P-450. On this basis it is practicable to convert the typical monooxygenase substrates into inducers of the enzyme biosynthesis by the blockage of the molecule site subjected to monooxygenation. A model is suggested which shows the phenobarbital participation in the formation of the specific configuration of the active site of cytochrome P-450 synthesized; the latter catalyzes the oxidation of a number of substrates by the way typical of inducer itself. |
