Decrease in hepatic cytochrome P-450 by cobalt. Evidence for a role of cobalt protoporphyrin.
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.
D000818:Animals; D002478:Cells, Cultured; D002642:Chick Embryo; D003035:Cobalt / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D006418:Heme / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D011166:Porphyrins / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D011524:Protoporphyrins / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D011166:Porphyrins; D011506:Proteins; D011524:Protoporphyrins; D003035:Cobalt; D006418:Heme; C007095:cobaltiprotoporphyrin; D003577:Cytochrome P-450 Enzyme System; C018021:cobaltous chloride