Identification and characterization of CYP2C18 in the cynomolgus macaque (Macaca fascicularis).
The macaque is widely used for investigation of drug metabolism due to its evolutionary closeness to the human. However, the genetic backgrounds of drug-metabolizing enzymes have not been fully investigated; therefore, identification and characterization of drug-metabolizing enzyme genes are important for understanding drug metabolism in this species. In this study, we isolated and characterized a novel cytochrome P450 2C18 (CYP2C18) cDNA in cynomolgus macaques. This cDNA was highly homologous (96%) to human CYP2C18 cDNA. Cynomolgus CYP2C18 was preferentially expressed in the liver and kidney. Moreover, a metabolic assay using cynomolgus CYP2C18 protein heterologously expressed in Escherichia coli revealed its activity toward S-mephenytoin 4'-hydroxylation. These results suggest that cynomolgus CYP2C18 could function as a drug-metabolizing enzyme in the liver.
Uno
Yasuhiro
Y
Pharmacokinetics and Bioanalysis Center (PBC), Shin Nippon Biomedical Laboratories (SNBL), Kainan, Wakayama 642-0017, Japan. uno-yasuhiro@snbl.co.jp
Matsuno
Kiyomi
K
Nakamura
Chika
C
Utoh
Masahiro
M
Yamazaki
Hiroshi
H
D000595:Amino Acid Sequence; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D005260:Female; D006801:Humans; D008099:Liver / Q000201:enzymology*; D008252:Macaca fascicularis / Q000378:metabolism*; D008297:Male; D008617:Mephenytoin / Q000378:metabolism*; D008969:Molecular Sequence Data; D010802:Phylogeny; D012313:RNA / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000662:veterinary; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA
D012313:RNA; D001189:Aryl Hydrocarbon Hydroxylases; D008617:Mephenytoin