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Modulation of rabbit and human hepatic cytochrome P-450-catalyzed steroid hydroxylations by alpha-naphthoflavone.

Authors
  • Schwab, G E
  • Raucy, J L
  • Johnson, E F
Type
Published Article
Journal
Molecular pharmacology
Publication Date
May 01, 1988
Volume
33
Issue
5
Pages
493–499
Identifiers
PMID: 3367901
Source
Medline
License
Unknown

Abstract

Rifampicin induces cytochrome P-450 3c, progesterone 16 alpha- and 6 beta-hydroxylation, 17 beta-estradiol 2-hydroxylation, benzo[a] pyrene hydroxylation, and erythromycin N-demethylation in rabbit liver microsomes. Kinetic analysis of the 6 beta-hydroxylation of progesterone as catalyzed by liver microsomes prepared from rifampicin-treated B/J rabbits exhibits a curvilinear double-reciprocal plot, suggestive of substrate activation. Further experimentation demonstrated that alpha-naphthoflavone could augment the catalytic efficiency [Vmax/Km] observed for the 16 alpha- and 6 beta-hydroxylation of progesterone and the 2-hydroxylation of 17 beta-estradiol, whereas erythromycin N-demethylase activity was partially inhibited. Allosteric activation of these steroid hydroxylases by alpha-naphthoflavone is also found for human liver microsomes, indicating that the activation of these enzymes is conserved in man and rabbit.

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