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CLONING CYP2D21 AND CYP3A22 CDNAS FROM LIVER OF MINIATURE PIGS

Tsutomu Sakuma, Tsukasa Shimojima, Kiyoshi Miwa and Tetsuya Kamataki
Drug Metabolism and Disposition April 2004, 32 (4) 376-378; DOI: https://doi.org/10.1124/dmd.32.4.376
Tsutomu Sakuma
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Tsukasa Shimojima
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Kiyoshi Miwa
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Tetsuya Kamataki
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Abstract

To compare the identity of the primary structure of drug-metabolizing cytochrome P450 between miniature pigs and humans, two cDNA clones, coding for miniature pig CYP2D21 and CYP3A22, were isolated. The deduced amino acid sequences of CYP2D21 and CYP3A22 were 78.3 and 75.0% identical to human CYP2D6 and CYP3A4, respectively. These values were nearly the same as those of bovine, dog, and some rodent isoforms, and 12.2 to 18.4% lower than those of nonhuman primates such as cynomolgus monkeys, Japanese monkey, and marmosets. These data indicate that miniature pig P450s are genetically not so close as monkey P450s to human P450s as previously expected. The recombinant CYP2D21 enzyme, however, showed bufuralol 1′-hydroxylase activity, suggesting that miniature pig CYP2D21 is capable of metabolizing some of the same substrates associated with human CYP2D6 despite its low identity to human counterparts.

Footnotes

  • ↵1 Abbreviations used are: P450, cytochrome P450; bp, base pairs; SRS, substrate recognition site.

  • ↵2 The P450s coded by MS2D and MS3A were designated as CYP2D21 and CYP3A22, respectively, by the cytochrome P450 nomenclature committee. The nucleotide sequences of CYP2D21 and CYP3A22 appear in the Genome Sequence DataBase, DNA DataBank of Japan, European Molecular Biology Laboratory, and National Center for Biotechnology Information databases with the accession numbers D89502 and AB006010, respectively.

  • This work was supported in part by a grant-in-aid for Scientific Research from the Ministry of Education, Sciences, Culture and Sports of Japan.

    • Received September 5, 2003.
    • Accepted January 7, 2004.
  • The American Society for Pharmacology and Experimental Therapeutics
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Drug Metabolism and Disposition: 32 (4)
Drug Metabolism and Disposition
Vol. 32, Issue 4
1 Apr 2004
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OtherShort Communication

CLONING CYP2D21 AND CYP3A22 CDNAS FROM LIVER OF MINIATURE PIGS

Tsutomu Sakuma, Tsukasa Shimojima, Kiyoshi Miwa and Tetsuya Kamataki
Drug Metabolism and Disposition April 1, 2004, 32 (4) 376-378; DOI: https://doi.org/10.1124/dmd.32.4.376

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OtherShort Communication

CLONING CYP2D21 AND CYP3A22 CDNAS FROM LIVER OF MINIATURE PIGS

Tsutomu Sakuma, Tsukasa Shimojima, Kiyoshi Miwa and Tetsuya Kamataki
Drug Metabolism and Disposition April 1, 2004, 32 (4) 376-378; DOI: https://doi.org/10.1124/dmd.32.4.376
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