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Biotransformation enzymes in human intestine: critical low levels in the colon?

W H Peters1, L Kock, F M Nagengast

  • 1Division of Gastrointestinal and Liver Diseases, St Radboud Hospital, Nijmegen, The Netherlands.

Gut
|April 1, 1991
PubMed

Insights

Drug-metabolising enzyme activity and isoenzyme profiles in the human intestine show significant regional differences. The colon exhibits lower enzyme activity and fewer isoenzymes compared to the small intestine, suggesting reduced detoxification capacity.

Area of Science:

  • Gastroenterology
  • Pharmacology
  • Biochemistry

Background:

  • Drug-metabolising enzymes are crucial for detoxifying harmful compounds in the gastrointestinal tract.
  • Understanding regional variations in enzyme activity is vital for assessing detoxification potential.
  • The human intestine exhibits distinct physiological and biochemical characteristics between the small and large bowel.

Purpose of the Study:

  • To investigate the activity and isoenzyme composition of key drug-metabolising enzyme systems in normal human small and large intestinal mucosa.
  • To compare the biotransformation capacity of the small intestine versus the colon.
  • To explore the implications of these differences for colonic carcinogenesis.

Main Methods:

  • Analysis of enzyme activity and isoenzyme profiles for glutathione S-transferase (GST), uridine diphosphate-glucuronosyltransferase (UGT), and cytochrome P-450 (CYP) in intestinal mucosal biopsies.
  • Utilisation of monoclonal antibodies for detecting specific protein bands of UGT and CYP enzymes.
  • Comparison of enzyme expression from proximal to distal small intestine and in the large intestine (colon).

Main Results:

  • A general decrease in drug-metabolising enzyme activity from the proximal to distal small intestine was observed.
  • A sharp decline in enzyme activity was noted in the large intestinal mucosa compared to the small intestine.
  • Significant alterations in isoenzyme composition were found: Alpha class GSTs were absent in the colon, while UGT and CYP enzyme expression (e.g., specific isoforms like P-450(4) and UGT 54 kDa) were reduced in the colon compared to the small intestine.

Conclusions:

  • The normal human colon possesses lower drug-metabolising enzyme activity and a reduced repertoire of isoenzymes compared to the small intestine.
  • This diminished enzymatic capacity in the colon may contribute to its higher susceptibility to carcinogenesis.
  • These findings highlight important regional differences in the gastrointestinal tract's detoxification capabilities.

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