Marmoset liver cytochrome P450s: study for expression and molecular cloning of their cDNAs.
Northern blot and immunoblot analyses indicated that considerable levels of CYP2B, CYP2C, CYP2D, CYP2E, and CYP3A were expressed in the liver of untreated marmosets. CYP1A was also expressed but to lesser extents. CYP3A mRNA was also detectable in the small intestine of untreated marmoset; the amount was increased by treatment with polychlorinated biphenyl. From a liver cDNA library, two cDNA clones coding for CYP2D19 and CYP3A21 (clones CM2D-1 and CM3A-10, respectively) were isolated. CM2D-1 and CM3A-10 contained an entire coding region for polypeptide 497 and 503 amino acid residues, respectively. The deduced amino acid sequences of CYP2D19 and CYP3A21 showed 90% identities to human CYP2D6 and CYP3A4, respectively. The value of CYP3A21 was 3% lower than that of cynomolgus monkey CYP3A8. On the other hand, these values were 11 to 23% higher than those of the other experimental animals, including dogs, rabbits, guinea pigs, rats, mice, and hamsters. These results indicate that the marmoset stands at a midpoint between human and nonprimate experimental animals.
Igarashi
T
T
Division of Drug Metabolism, Faculty of Pharmaceutical Sciences, Hokkaido University, Japan.
Sakuma
T
T
Isogai
M
M
Nagata
R
R
Kamataki
T
T
D000595:Amino Acid Sequence; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D001483:Base Sequence; D015153:Blotting, Western; D002144:Callithrix / Q000378:metabolism*; D002417:Cattle; D003001:Cloning, Molecular; D006224:Cricetinae; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism*; D018076:DNA, Complementary / Q000235:genetics; D004285:Dogs; D005260:Female; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D006168:Guinea Pigs; D006801:Humans; D051379:Mice; D008862:Microsomes, Liver / Q000201:enzymology*; D008969:Molecular Sequence Data; D008970:Molecular Weight; D011817:Rabbits; D051381:Rats; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid
D018076:DNA, Complementary; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; C105144:cytochrome P-450 CYP2D19 (marmoset); C105145:cytochrome P-450 CYP3A21 (marmoset)