Reconstituted liver microsomal enzyme system that hydroxylates drugs, other foreign compounds and endogenous substrates: I. Determination of substrate specificity by the cytochrome P-450 and P-448 fractions

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Abstract

The reconstituted microsomal hydroxylation enzyme system from rats treated with phenobarbital exhibited high activity for benzphetamine N-demethylation, but very low activity for 3,4-benzpyrene hydroxylation. However, when the cytochrome P-450 fraction from phenobarbital-treated rats was replaced by the cytochrome P-448 fraction from rats treated with 3-methylcholanthrene, the N-demethylation of benz-phetamine was decreased while the hydroxylation of 3,4-benzpyrene was greatly increased. On the other hand, the reconstituted system from 3-methylcholanthrene-treated rats showed good benzpyrene hydroxylase activity which could be greatly decreased if the cytochrome P-448 fraction was replaced by the P-450 fraction from rats treated with phenobarbital. These and other experiments indicate that the substrate specificity of the hydroxylation system resides in the cytochrome fraction rather than in the reductase or lipid fraction, and the data suggest that cytochromes P-450 and P-448 have different catalytic activities.

References (27)

  • M. Klingenberg

    Arch. Biochem. Biophys

    (1958)
  • D. Garfinkel

    Arch. Biochem. Biophys

    (1958)
  • T. Omura et al.

    J. Biol. Chem

    (1964)
  • Y. Imai et al.

    Biochem. Biophys. Res. Comm

    (1966)
  • A.H. Conney et al.

    J. Biol. Chem

    (1968)
  • A.H. Conney et al.
  • A.P. Alvares et al.

    Biochem. Biophys. Res. Comm

    (1967)
  • R. Kuntzman et al.

    Life Sciences

    (1968)
  • N.E. Sladek et al.

    Biochem. Biophys. Res. Comm

    (1966)
  • A. Hildebrandt et al.

    Biochem. Biophys. Res. Comm

    (1968)
  • W. Levin et al.

    J. Biol. Chem

    (1969)
  • A.Y.H. Lu et al.

    J. Biol. Chem

    (1968)
  • A.Y.H. Lu et al.

    J. Biol. Chem

    (1969)
  • Cited by (0)

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