Abstract
Cytochrome P450 (CYP or P450) 3A4 is known to be the major P450 expressed 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 metabolism 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 from hepatic cDNA. To investigate whether intestinal and hepatic CYP3A4 enzymes are identical, we determined the sequences of intestinal CYP3A4 cDNAs. Compared with the published sequence for hepatic CYP3A4, we found a single base pair difference in the 3′ untranslated region of intestinal cDNA from three individuals. We found this same base pair difference 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.
Footnotes
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Send reprint requests to: Paul B. Watkins, 1500 East Medical Center Drive, University of Michigan Medical Center, Room A7119-UH, Ann Arbor, MI 48109-0108.
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This study was supported by National Institute of General Medical Sciences Grants GM53095 (K.S.L.) and GM38149 (P.B.W.).
- Abbreviations used are::
- P450 or CYP
- cytochrome P450
- PCR
- polymerase chain reaction
- Received July 24, 1997.
- Accepted October 22, 1997.
- The American Society for Pharmacology and Experimental Therapeutics
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