Turnover of messenger RNA, apoprotein and haem of cytochrome P-450b + e induced by phenobarbitone in rat liver

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Abstract
A single injection of phenobarbitone elicits asynchronous behavior in the pattern of induction of mRNA, apoprotein and heme of cytochrome P-450b + e. The mRNA content reaches a maximum around 16 h, the apoprotein content reaches a maximum around 30-36 h, and the holoprotein content shows biphasic behavior, with maxima around 16 h and 30-36 h. With the use of CoCl2 to block fresh transcription of cytochrome P-450b + e mRNA, the half-life of the preinduced mRNA was found to be 3 h. The apoprotein and heme moieties of cytochrome P-450b + e turn over with half-lives of 16 h and 8 h, respectively. The pattern of induction of .delta.-aminolevulinate synthase shows biphasic behavior, with maxima around 16 h and 30-36 h. The biphasic behavior of the holoprotein content is thus due to differences in the extent of saturation of the apoprotein with heme, the process being regulated by the activity of the rate-limiting .delta.-aminolevulinate synthase and the independent faster turnover rate of heme with respect to the apoprotein. Massive degradation of the heme moiety of preformed cytochrome P-450b + e results in the subsequent degradation of the apoprotein.