PMID: 2494942Apr 1, 1989Paper

Selective potent restriction of P450b- but not P450e-dependent 7,12-dimethylbenz[a]anthracene metabolism by the microsomal environment

Archives of Biochemistry and Biophysics
M ChristouC R Jefcoate

Abstract

The prototypic members of the rat liver cytochrome P450IIB subfamily, P450b and P450e, differ by only 13 amino acids and yet purified P450b is considerably more active than P450e for all known substrates. A unique regioselectivity difference between cytochromes P450b and P450e for the metabolism of 7,12-dimethylbenz[a]anthracene (DMBA) and a genetic deficiency in P450e expression in the Marshall (M520/N) rat strain have been exploited to determine the microsomal contributions of the respective forms toward the metabolism of DMBA. The total contribution to metabolism by each isozyme has been assessed based on the sensitivity to rabbit anti-P450b/e IgG and comparison with microsomal P450b and P450e content as measured by Western blots. Liver microsomes from untreated M520/N rats do not express detectable levels of P450e but express P450b at a level that is 2-fold higher than that of P450e in liver microsomes from untreated F344 rats (50 pmol/mg). However, only 4% of the constitutive DMBA metabolizing activity of liver microsomes from the M520/N rat strain could be inhibited by anti-P450b/e IgG. A 30-fold induction of hepatic P450b by phenobarbital (PB) was also completely ineffective in increasing P450b-dependent DMBA metabolism....Continue Reading

References

Nov 1, 1987·Archives of Biochemistry and Biophysics·M ChristouC R Jefcoate
Aug 1, 1987·Molecular Endocrinology·B J SongF J Gonzalez
Jan 1, 1987·Annual Review of Biochemistry·D W Nebert, F J Gonzalez
Aug 1, 1987·Biochemical Genetics·A Rampersaud, F G Walz
Jan 1, 1986·CRC Critical Reviews in Biochemistry·M Adesnik, M Atchison
Feb 1, 1987·DNA·D W NebertW Levin
Nov 1, 1985·Archives of Biochemistry and Biophysics·L M ReikP E Thomas
Jul 15, 1985·Biochemical Pharmacology·S F PikeI R Phillips
May 1, 1982·Proceedings of the National Academy of Sciences of the United States of America·Y Fujii-KuriyamaM Muramatsu

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Citations

Jul 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·T AoyamaF J Gonzalez
Dec 31, 1997·Microscopy Research and Technique·K J Rich, A R Boobis

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