Biotransformation of xenobiotics in human intestinal mucosa

Drug-metabolizing enzymes, especially monooxygenases, play a major role in biotransformation and detoxification of many foreign compounds including environmental carcinogens. Although largely localized in the liver they are also found in the small intestine, which is the portal of entry of dietary toxins. Therefore cytochrome P-450 content as well as monooxygenase (7-ethoxycoumarin O-deethylase) and NADPH-cytochrome c reductase activities were determined in surgical specimens of the human small intestine and in jejunal biopsy material obtained from patients by use of a hydraulic biopsy instrument. Microsomes were prepared from surgical material; these ranged in P-450 content from 30 to 120 pmole/mg protein and in monooxygenase activity from 60 to 110 pmole/min-mg protein. In the 20,000g supernatant of the homogenized biopsy material, monooxygenase activity was undetectable in patients who had total villous atrophy, and low enzyme rates were found when the mucosa showed a partial villous atrophy. The mucosal monooxygenase activity of patients with normal jejunal histology and steatorrhea was significantly higher than in mucosa with villous atrophy but was only half of that observed in normal controls. These eight control patients had normal histology and no malassimilation. Our results suggest that monooxygenase activity in the human small intestine is dependent on the morphological integrity of the mucosa and that in normal mucosa the enzyme rates are reduced when malassimilation is present.