[Factors regulating mono-oxygenase induction by phenobarbital xenobiotics].
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.
D000632:Aminopyrine / Q000378:metabolism / Q000494:pharmacology; D000654:Amobarbital / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001711:Biotransformation; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004790:Enzyme Induction; D008297:Male; D008748:Methylcholanthrene / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008862:Microsomes, Liver / Q000201:enzymology*; D010634:Phenobarbital / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D000632:Aminopyrine; D008748:Methylcholanthrene; D003577:Cytochrome P-450 Enzyme System; D000654:Amobarbital; D010634:Phenobarbital
Faktory, reguliruiushchie induktsiiu monooksigenaz ksenobiotikami fenobarbitalovogo riada.