Distribution of cytochrome P450 2C, 2E1, 3A4, and 3A5 in human colon mucosa

Expression of CYP2C, CYP2E1, CYP3A4, and CYP3A5 mRNA in colon mucosa was determined by RT-PCR. Protein concentration of CYPs was determined using Western blot methods.Extensive interindividual variability was found for the expression of most of the genes. However, expression of CYP2C mRNA levels were significantly higher in the ascending colon than in the sigmoid colon. In contrast, mRNA levels of CYP2E1 and CYP3A5 were significantly lower in the ascending colon in comparison to the descending and sigmoid colon. In sigmoid colon protein levels of CYP2C8 were significantly higher by ~73% than in the descending colon. In contrast, protein concentration of CYP2E1 was significantly lower by ~81% in the sigmoid colon in comparison to the descending colon.The current data suggest that the expression of CYP2C, CYP2E1, and CYP3A5 varies in different parts of the colon.Throughout the last decades drug metabolism in the alimentary tract has received growing attention as part of the body's first line of defense against orally ingested harmful xenobiotica. Most xenobiotic compounds require an enzymatic activation to form a carcinogen or toxicant. The reactive intermediates resulting form enzymatic drug metabolism are often unstable and therefore are unlikely to be transported from the liver to other tissues to exert toxicity. Therefore, the chemical toxicity found in extrahepatic tissue often results from cellular metabolic activities in the organ. However, knowledge on the variability and regulation of expression of drug metabolizing enzymes in the human gastrointestinal tract and particularly the large intestine is poor in comparison with the "classical" drug metabolizing organs (e.g. liver).Cytochrome P450 (CYP) is a multi-gene superfamily of heme-containing enzymes catalyzing the oxidative metabolism of many compounds [1]. CYP families 1, 2, and 3, which are the main CYP families participating in the metabolism of xenobiotics, are highly expressed within the liver, but are