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Decrease in hepatic cytochrome P-450 by cobalt. Evidence for a role of cobalt protoporphyrin.

J F Sinclair·P R Sinclair·J F Healey·E L Smith·H L Bonkowsky
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Abstract

Exposure of cultured chick-embryo hepatocytes to increasing concentrations of CoCl2 in the presence of allylisopropylacetamide results in formation of cobalt protoporphyrin, with a reciprocal decrease in haem and cytochrome P-450. Treatment of rats with CoCl2 (84 mumol/kg) and 5-aminolaevulinate (0.2 mmol/kg) also results in formation of cobalt protoporphyrin and a decrease in cytochrome P-450 in the liver. Hepatic microsomal fractions from rats treated with phenobarbital, CoCl2 and 5-aminolaevulinate were analysed by polyacrylamide gel electrophoresis. Cobalt protoporphyrin was associated mainly with proteins of 50000-53000 mol.wt. The results suggest that the formation of cobalt protoporphyrin occurred at the expense of the synthesis of haem, leading to a decrease in cytochrome P-450. Furthermore, the cobalt protoporphyrin that was formed may itself have been incorporated into apocytochrome P-450.

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AnimalsCells, CulturedChick EmbryoCobaltCytochrome P-450 Enzyme SystemElectrophoresis, Polyacrylamide GelHemeLiverMaleMicrosomes, LiverPorphyrinsProteinsProtoporphyrinsRatsRats, Inbred StrainsJournal ArticleResearch Support, U.S. Gov't, Non-P.H.S.Research Support, U.S. Gov't, P.H.S.

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J F Sinclair, P R Sinclair, J F Healey, E L Smith, H L Bonkowsky. 1982-04-15. Decrease in hepatic cytochrome P-450 by cobalt. Evidence for a role of cobalt protoporphyrin.. https://doi.org/10.1042/bj2040103

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