title: Identification and characterization of CYP2C18 in the cynomolgus macaque (Macaca fascicularis).
abstract: 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.
authors: Pharmacokinetics and Bioanalysis Center (PBC), Shin Nippon Biomedical Laboratories (SNBL), Kainan, Wakayama 642-0017, Japan. uno-yasuhiro@snbl.co.jp
authors: Yasuhiro
authors: Y
authors: Uno
authors: Kiyomi
authors: K
authors: Matsuno
authors: Chika
authors: C
authors: Nakamura
authors: Masahiro
authors: M
authors: Utoh
authors: Hiroshi
authors: H
authors: Yamazaki
mesh_terms: 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
chemical_list: D012313:RNA; D001189:Aryl Hydrocarbon Hydroxylases; D008617:Mephenytoin