PMID: 2117439Jul 15, 1990Paper

Inhibition of uroporphyrinogen decarboxylase activity. The role of cytochrome P-450-mediated uroporphyrinogen oxidation

The Biochemical Journal
R W LambrechtJ F Sinclair

Abstract

It was previously shown that uroporphyrinogen oxidation is catalysed by a form of cytochrome P-450 induced by 3-methylcholanthrene [Sinclair, Lambrecht & Sinclair (1987) Biochem. Biophys. Res. Commun. 146, 1324-1329]. We have now measured uroporphyrinogen oxidation and uroporphyrinogen decarboxylation simultaneously in 10,000 g supernatants from the livers of methylcholanthrene-treated mice and chick embryos incubated with an NADPH-generating system. We found that uroporphyrinogen oxidation is associated with inhibition of uroporphyrinogen decarboxylase activity. The decreased uroporphyrinogen decarboxylase activity was not due to depletion of substrate, since decarboxylase activity was not increased by a 2.6-fold increase in uroporphyrinogen. Uroporphyrinogen oxidation and the associated inhibition of decarboxylase activity were also observed with liver supernatant from methylcholanthrene-treated chick embryo; both actions required the addition of 3,3',4,4'-tetrachlorobiphenyl. Uroporphyrinogen oxidation catalysed by microsomes from a methylcholanthrene-treated mouse inhibited the uroporphyrinogen decarboxylase activity in the 100,000 g supernatant. Ketoconazole, an inhibitor of cytochrome P-450, prevented both uroporphyrinoge...Continue Reading

Citations

Jan 24, 2003·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Peter R SinclairGlenn S Gerhard
Apr 1, 1995·Journal of Bioenergetics and Biomembranes·G H Elder, A G Roberts
Oct 27, 2001·Clinical and Experimental Immunology·Y MaS Fargion
Oct 29, 2008·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Kenzi NakanoShoichi Fujita
Dec 26, 2006·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Nadia GormanPeter R Sinclair
Sep 15, 2007·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Nadia GormanPeter R Sinclair
Mar 27, 2002·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Nadia GormanPeter R Sinclair
May 1, 2001·Current Protocols in Toxicology·J D Phillips, J P Kushner
Jan 1, 1990·Journal of Biochemical Toxicology·J M JacobsN J Jacobs
Sep 24, 2004·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Nadia GormanPeter R Sinclair
Jan 13, 2000·Toxicology and Applied Pharmacology·P R SinclairD W Nebert
May 23, 2001·Archives of Biochemistry and Biophysics·P R SinclairJ F Sinclair
Nov 18, 2000·Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP· De Catabbi SCBL C de Viale
Feb 11, 1999·Comparative Biochemistry and Physiology. Part C, Pharmacology, Toxicology & Endocrinology·N GormanP R Sinclair
Jun 15, 1991·Biochemical Pharmacology·S Deam, G H Elder
May 1, 1992·Archives of Biochemistry and Biophysics·R W LambrechtJ F Sinclair
May 1, 2007·Toxicology and Applied Pharmacology·Nadia GormanPeter R Sinclair

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