SEQUENCES OF INTESTINAL AND HEPATIC CYTOCHROME-P450 3A4 CDNAS ARE IDENTICAL

Cytochrome P450 (CYP or P450) 3A4 is known to be the major P450 expres sed in the liver. More recently, CYP3A4 was also shown to be the major P450 in the intestine, where it plays an important role in the metabo lism of some orally administered drugs. However, studies examining the catalytic properties of CYP3A4 have been largely based on the use of CYP3A4 enzyme obtained from liver or recombinant protein expressed fro m hepatic cDNA. To investigate whether intestinal and hepatic CYP3A4 e nzymes are identical, we determined the sequences of intestinal CYP3A4 cDNAs. Compared with the published sequence for hepatic CYP3A4, we fo und a single base pair difference in the 3' untranslated region of int estinal cDNA from three individuals. We found this same base pair diff erence in cDNA obtained from the livers of three additional subjects. We conclude that hepatic and intestinal CYP3A4 cDNAs are identical and that the proteins expressed in these two tissues are therefore likely to be the same.