Characterization of cynomolgus monkey cytochrome P450 (CYP) cDNAs: is CYP2C76 the only monkey-specific CYP gene responsible for species differences in drug metabolism?
Cynomolgus monkey CYP2C76 does not have a corresponding ortholog in humans, and it is at least partly responsible for differences in drug metabolism between monkeys and humans. To determine if CYP2C76 is the only monkey-specific CYP gene, we identified cynomolgus monkey cDNAs for CYP2A23, CYP2A24, CYP2E1, CYP2J2, CYP3A5, CYP3A8, CYP4A11, CYP4F3, CYP4F11, CYP4F12, and CYP4F45. These CYP cDNAs showed a high sequence identity (93-96%) to the homologous human CYP cDNAs. The monkey CYPs were preferentially expressed in liver among the analyzed tissues. Moreover, all five analyzed monkey CYPs (CYP2A23, CYP2A24, CYP2E1, CYP3A5, and CYP3A8) metabolized typical substrates for human CYPs in the corresponding subfamilies. These results suggest that these 11 monkey CYP cDNAs are closely related to the human CYP cDNAs and thus, unlike CYP2C76, are not apparent monkey-specific cDNAs.
Uno
Yasuhiro
Y
Laboratory of Translational Research, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita 14 Nishi 6, Kita-ku, Sapporo 060-0812, Japan. uno-yasuhiro@snbl.co.jp
Hosaka
Shinya
S
Matsuno
Kiyomi
K
Nakamura
Chika
C
Kito
Go
G
Kamataki
Tetsuya
T
Nagata
Ryoichi
R
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry* / Q000502:physiology*; D018076:DNA, Complementary / Q000235:genetics; D006801:Humans; D008252:Macaca fascicularis; D008969:Molecular Sequence Data; D009928:Organ Specificity; D017385:Sequence Homology; D013045:Species Specificity; D014018:Tissue Distribution
D018076:DNA, Complementary; C400322:cytochrome P-450 CYP2C subfamily; D003577:Cytochrome P-450 Enzyme System