THE HUMAN INTESTINAL CYTOCHROME P450 “PIE”
Top Cited Papers
- 1 May 2006
- journal article
- Published by Elsevier in Drug Metabolism and Disposition
- Vol. 34 (5) , 880-886
- https://doi.org/10.1124/dmd.105.008672
Abstract
Cytochromes P450 (P450s) 3A, 2C, and 1A2 constitute the major “pieces” of the human liver P450 “pie” and account, on average, for 40, 25, and 18%, respectively, of total immunoquantified P450s (J Pharmacol Exp Ther 270:414–423, 1994). The P450 profile in the human small intestine has not been fully characterized. Therefore, microsomes prepared from mucosal scrapings from the duodenal/jejunal portion of 31 human donor small intestines were analyzed by Western blot using selective P450 antibodies. P450s 3A4, 2C9, 2C19, and 2J2 were detected in all individuals and ranged from 8.8 to 150, 2.9 to 27, 2J2 > 2D6 (8.4, 1.1, 0.9, and 0.5 pmol/mg, respectively). Analysis of a pooled preparation of the 31 donor specimens substantiated these results. In summary, as in the liver, large interindividual variation exists in the expression levels of individual P450s. On average, CYP3A and CYP2C9 represents the major pieces of the intestinal P450 pie, accounting for 80 and 15%, respectively, of total immunoquantified P450s.Keywords
This publication has 39 references indexed in Scilit:
- DO MEN AND WOMEN DIFFER IN PROXIMAL SMALL INTESTINAL CYP3A OR P-GLYCOPROTEIN EXPRESSION?Drug Metabolism and Disposition, 2005
- IN VITRO SULFOXIDATION OF THIOETHER COMPOUNDS BY HUMAN CYTOCHROME P450 AND FLAVIN-CONTAINING MONOOXYGENASE ISOFORMS WITH PARTICULAR REFERENCE TO THE CYP2C SUBFAMILYDrug Metabolism and Disposition, 2004
- CYP2C subfamily, primarily CYP2C9, catalyses the enantioselective demethylation of the endocrine disruptor pesticide methoxychlor in human liver microsomes: use of inhibitory monoclonal antibodies in P450 identificationXenobiotica, 2004
- THE SMALL INTESTINE AS A XENOBIOTIC-METABOLIZING ORGANDrug Metabolism and Disposition, 2003
- Interindividual Variability in Inhibition and Induction of Cytochrome P450 EnzymesAnnual Review of Pharmacology and Toxicology, 2001
- Clinical Pharmacokinetics of FluvastatinClinical Pharmacokinetics, 2001
- P450 SUBFAMILY CYP2J AND THEIR ROLE IN THE BIOACTIVATION OF ARACHIDONIC ACID IN EXTRAHEPATIC TISSUES*Drug Metabolism Reviews, 1999
- First-pass metabolism of cyclosporin by the gutThe Lancet, 1991
- Cloning and expression of complementary DNAs for multiple members of the human cytochrome P450IIC subfamilyBiochemistry, 1991
- Identification of glucocorticoid-inducible cytochromes P-450 in the intestinal mucosa of rats and man.Journal of Clinical Investigation, 1987