Immunochemical studies on the metabolism of nitrosamines by ethanol-inducible cytochrome P-450

Chung S. Yang, Dennis Koop, Tianyuan Wang, Minor J. Coon

Research output: Contribution to journalArticle

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Abstract

The ethanol-induced rabbit liver microsomal cytochrome P-450, P-450LM3a, has been shown previously to efficiently catalyze the demethylation of N-nitrosodimethylamine (NDMA) with a Km of 2.9 mM. Since the predominant Km in hepatic microsomes from ethanol-treated rabbits is 0.07 mM, the role of P-450LM3a in the activation of this carcinogen has been uncertain. In the present study, antibodies to P-450LM3a were shown to almost completely inhibit NDMA demethylation by the purified P-450 in a reconstituted system as well as the low-Km activity of liver microsomes from control or ethanol-treated rabbits. In contrast, the antibody did not inhibit the high-Km NDMA demethylase activity in the microsomes. These results indicate that P-450LM3a is the major P-450 responsible for the low-Km NDMA demethylase activity. In addition, evidence is provided for the existence of a cytochrome immunochemically similar to P-450LM3a in liver microsomes from rats, mice, and guinea pigs that effectively catalyzes the demethylation of NDMA.

Original languageEnglish (US)
Pages (from-to)1007-1013
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume128
Issue number2
DOIs
StatePublished - Apr 30 1985
Externally publishedYes

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Dimethylnitrosamine
Nitrosamines
Metabolism
Liver
Cytochrome P-450 Enzyme System
Cytochrome P-450 CYP2E1
Ethanol
Liver Microsomes
Microsomes
Rabbits
Antibodies
Cytochromes
Carcinogens
Rats
Guinea Pigs
Chemical activation

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Immunochemical studies on the metabolism of nitrosamines by ethanol-inducible cytochrome P-450. / Yang, Chung S.; Koop, Dennis; Wang, Tianyuan; Coon, Minor J.

In: Biochemical and Biophysical Research Communications, Vol. 128, No. 2, 30.04.1985, p. 1007-1013.

Research output: Contribution to journalArticle

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