Effects of linoleic acid hydroperoxide on the hepatic monooxygenase systems of microsomes from untreated, phenobarbital treated, and 3-methylcholanthrene treated rats

E. Jeffery, A. Kotake, R. El Azhary, G. J. Mannering

Research output: Contribution to journalArticle

Abstract

Increasing concentrations of linoleic acid hydroperoxide (10-250 μM) destroyed increasing amounts of P 450 hemoprotein in hepatic microsomes from untreated, phenobarbital treated, and 3 methylcholanthrene treated rats. Loss of P 450 hemoprotein in microsomes from untreated and phenobarbital treated rats was biphasic; 50% was destroyed at low concentrations of linoleic acid hydroperoxide (50 μM or less), and only about half the remainder was destroyed at relatively high concentrations (150 μM or more). The labile population of P 450 hemoprotein was designated P 450(ll), and the stable, P 450(ls). The loss of P 450 hemoprotein in microsomes from 3 methylcholanthrene treated rats was not biphasic, and most of the hemoprotein was in the stable form. Almost all of the monooxygenase activity (ethylmorphine N demethylase, aniline hydroxylase) and type I binding (hexobarbital) was associated with P 450(ll). Microsomal NADPH cytochrome c reductase activities and cytochrome b5 levels were not affected by linoleic acid hydroperoxide until high concentrations were reached (150 μM or more). NADH cytochrome c reductase activity was similarly unaffected by linoleic acid hydroperoxide in microsomes from untreated rats, was slightly elevated in microsomes from 3 methylcholanthrene treated rats, and was greatly elevated in microsomes from phenobarbital treated rats. NADPH oxidase activity was unaffected by linoleic acid hydroperoxide in microsomes from untreated and 3 methylcholanthrene treated rats, but was decreased slightly in microsomes from phenobarbital treated animals. These results led to the conclusion that P 450(ll) functions in the oxidation of exogenous substrates, that P 450(ls) functions in the oxidation of endogenous substrates, and that the 2 functions are essentially independent of each other.

Original languageEnglish (US)
Pages (from-to)415-425
Number of pages11
JournalMolecular Pharmacology
Volume13
Issue number3
StatePublished - Dec 1 1977
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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