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Small intestinal cytochromes P450.

L S Kaminsky1, M J Fasco

  • 1Wadsworth Center for Laboratories and Research, New York State Department of Health, Albany 12201-0509.

Critical Reviews in Toxicology
|January 1, 1991
PubMed
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Small intestinal cytochromes P450 (P450) are crucial for metabolizing ingested substances, leading to either detoxification or harmful bioactivation. Diet significantly impacts P450 levels and activity, with implications for gastrointestinal health and cancer risk.

Area of Science:

  • Pharmacology and Toxicology
  • Gastroenterology
  • Biochemistry

Background:

  • Small intestinal cytochromes P450 (P450) are primary enzymes for xenobiotic biotransformation.
  • Their activity can result in either detoxification or bioactivation of ingested compounds.
  • P450 concentrations vary along the small intestine and villus, with specific forms identified in humans and various animal models.

Purpose of the Study:

  • To review the distribution, induction, and dietary modulation of small intestinal P450 enzymes.
  • To explore the role of intestinal P450 in xenobiotic metabolism and its potential link to gastrointestinal pathologies.

Main Methods:

  • Literature review of studies on small intestinal P450 distribution, enzyme kinetics, and induction.
  • Analysis of experimental data on the effects of xenobiotics and dietary factors on P450 activity.

Related Experiment Videos

  • Examination of substrates like aryl hydrocarbon hydroxylase (AHH), 7-ethoxycoumarin O-deethylase (ECOD), and 7-ethoxyresorufin O-deethylase (EROD) to characterize P450s.

    • Main Results:

    • P450s are most concentrated in the duodenum and decrease distally, with highest levels in midvillus to villous tip.
    • Intestinal P450s are inducible by xenobiotics, with oral administration being most effective and rapid.
    • Dietary factors profoundly affect P450s: iron restriction decreases activity, Brussels sprouts and fried meat increase activity, and vitamin A and cholesterol levels modulate activity.

    Conclusions:

    • Intestinal P450s play a significant role in xenobiotic metabolism, with variable distribution and susceptibility to induction and dietary influences.
    • While direct links to specific xenobiotic toxification are limited, elevated intestinal P450 levels are indirectly associated with gastrointestinal cancer.
    • Intestinal metabolism of certain compounds, like 2,2,2-trifluoroethanol, can lead to direct intestinal damage and subsequent infection.