Turnover of Two Drug-Inducible Forms of Microsomal Cytochrome P-450 in Rat Liver1

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Abstract
The turnover of two forms of cytochrome P-450, phenobarbital (PB) inducible form (P-450(PB)) and 3-methylcholanthrene inducible form (P-450(MC)), as well as NADPH-cytochrome P-450 reductase (fp T ) and cytochrome b5 in rat liver was studied. 14 C-Labeled DL-leucine, sodium bicarbonate, or δ-aminolevulinic acid was given to normal and inducer-treated rats, and the subsequent decay of the radioactivities was measured to calculate the half-lives of the microsomal proteins. The half-lives of the proteins of P-450(PB), P-450(MC), fP T , and cytochrome b5 in the liver of normal rats were 30, 15, 50, and 80 h, respectively, with [ 14 C]leucine and 25, 15, 35, and 50 h, respectively, with sodium [ 14 C]bicarbonate. These data indicate that the two forms of cytochrome P-450 turn over at different rates, and their half-lives are shorter than those of the other components of the microsomal monooxygenase system. The use of radioactive bicarbonate showed that the observed turnover rates of P-450(PB) and P-450(MC) were little affected whereas those of fp T and cytochrome b5 which turn over relatively slowly, were more significantly affected by the re-utilization of the amino acid when radioactive leucine was used. The half-lives of the proteins of P-450(PB), P-450(MC), fp T , and cytochrome b 5 in the liver of PB-treated rats were 20, 20, 25, and 30 h, respectively, with radioactive bicarbonate. Apparently, PB has no stabilizing effect on the turnover of the microsomal proteins examined. The turnover of fp T and cytochrome b5 was rather stimulated by PB treatment and the half-lives became closer to those of P-450(PB) and P-450(MC), indicating a possible simultaneous degradation of microsomal membrane constituents in the liver of PB-treated rats. The half-lives of the heme of P-450(PB), P-450(MC), and cytochrome b5 in the liver of normal rats were 15, 15, and 40 h, respectively, when radioactive δ-aminolevulinic acid was used. The heme of P-450(PB) was apparently dissociable and turned over faster than its protein moiety, whereas the heme and protein portions of P-450(MC) and cytochrome b5 turned over at almost identical rates.