Purification and characterization of an acetone-inducible cytochrome P-450 from hamster liver microsomes

Biochem J. 1992 Nov 1;287 ( Pt 3)(Pt 3):863-70. doi: 10.1042/bj2870863.

Abstract

A form of cytochrome P-450 has been purified to electrophoretic homogeneity from the hepatic microsomes of Syrian golden hamsters treated with acetone. This P-450 form, designated ha P-450j, had an M(r) of approximately 55,000, bound dimethyl sulphoxide and exhibited a CO-reduced absorbance maximum at 451 nm. The absolute spectra of its oxidized form indicated that ha P-450j was predominantly in the low-spin state. In a reconstituted system, ha P-450j showed relatively low catalytic activities towards 7-ethoxycoumarin, 7-ethoxyresorufin, aminopyrine, ethylmorphine and benzphetamine, whereas it catalysed the oxidation of aniline, acetone and thiobenzamide with a high catalytic-centre activity. In addition, ha P-450j catalysed at a high rate the high-affinity component of dimethylnitrosamine N-demethylase; in contrast, only the low-affinity component of diethylnitrosamine N-de-ethylase was efficiently catalysed. The addition of cytochrome b5 to the reconstitution system decreased the Km value for dimethylnitrosamine N-demethylase by a factor of 5 and increased the Vmax. value, and slightly enhanced the other activities. Thiobenzamide and diethyldithiocarbamate were found to be the most effective inhibitors of the ha-P-450j-dependent aniline hydroxylation. Polyclonal antibodies against rat P-450j recognized ha P-450j in immunoblots of control and treated hamster liver microsomes. Treatment of hamsters with acetone increased the apparent abundance of ha P-450j in microsomes, whereas phenobarbital and beta-naphthoflavone did not induce it. Analysis of N-terminal amino acid sequences demonstrated that ha P-450j has a high degree of sequence identity with rat P-450j. All the evidence presented in this study indicates that ha P-450j could represent the hamster orthologue of the previously described CYP2E1(s) of other species.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetone / pharmacology*
  • Amino Acid Sequence
  • Aniline Compounds / metabolism
  • Animals
  • Blotting, Western
  • Cricetinae
  • Cytochrome P-450 CYP2E1
  • Cytochrome P-450 Enzyme System / isolation & purification
  • Cytochrome P-450 Enzyme System / metabolism*
  • Enzyme Induction / drug effects
  • Humans
  • Hydroxylation
  • Kinetics
  • Male
  • Mesocricetus
  • Microsomes, Liver / drug effects
  • Microsomes, Liver / enzymology*
  • Molecular Sequence Data
  • Oxidoreductases, N-Demethylating / metabolism
  • Sequence Homology, Amino Acid
  • Spectrum Analysis

Substances

  • Aniline Compounds
  • Acetone
  • Cytochrome P-450 Enzyme System
  • Cytochrome P-450 CYP2E1
  • Oxidoreductases, N-Demethylating
  • aniline