PMID: 8963944Jan 1, 1996Paper

Cytochrome P450 and its interactions with the heme biosynthetic pathway

Canadian Journal of Physiology and Pharmacology
F De Matteis, G S Marks

Abstract

An important factor in disruption of hepatic heme biosynthesis by porphyrinogenic drugs appears to be interaction with one or several cytochrome P450 isozymes. Clarification of the nature of the interaction between porphyrinogenic drugs and cytochrome P450 isozymes, as well as identification of the isozymes involved, will be helpful in extrapolating the results of animal experimentation to humans. Administration of griseofulvin to mice results in accumulation in the liver of two N-alkylated protoporphyrins (PPs). The major N-alkyl PP, N-griseofulvin PP, which is devoid of ferrochelatase-inhibitory activity, was shown to be the precursor of N-methyl PP, which is a potent ferrochelatase inhibitor. N-Griseofulvin PP was present predominantly as the Nc regioisomer rather than the anticipated NA regioisomer. Progesterone (PG) 6 beta-hydroxylase and androstenedione (AD) 6 beta-hydroxylase, diagnostic markers for cytochrome P450 3A1/2 activity in rat liver, were identified in chick embryo liver. The in ovo administration of 3,5-diethoxycarbonyl-1,4-dihydro-2,6-dimethyl-4-ethylpyridine (4-ethyl DDC) and 3-[2-(2,4,6-trimethylphenyl)thioethyl]-4-methylsydnone (TTMS) caused inactivation of chick embryo hepatic PG and AD 6 beta-hydroxylase...Continue Reading

Citations

Jan 1, 2003·Environmental Health and Preventive Medicine·Shigeru Sassa
Jan 24, 2003·Annual Review of Pharmacology and Toxicology·Michael S Denison, Scott R Nagy
Nov 26, 2005·Biological Chemistry·Ralf P MeyerUrs A Meyer
Jun 29, 2014·Toxicological Sciences : an Official Journal of the Society of Toxicology·Jean-Marie NicolasSophie Kervyn
Aug 21, 2013·Trends in Endocrinology and Metabolism : TEM·Marina BayevaHossein Ardehali
Jun 1, 2005·Experimental and Molecular Pathology·Fawzia Bardag-GorceSamuel W French
Feb 15, 2001·Experimental and Molecular Pathology·F Bardag-GorceS W French
Mar 6, 2010·Expert Opinion on Drug Metabolism & Toxicology·Ralf Peter Meyer, Marcel Gehlhaus
Jan 1, 1999·Biomarkers : Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals· T Berbner N Rahman T Braunbeck

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