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

Abstract

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