Uno Yasuhiro, Matsuno Kiyomi, Nakamura Chika, Utoh Masahiro, Yamazaki Hiroshi
Pharmacokinetics and Bioanalysis Center (PBC), Shin Nippon Biomedical Laboratories (SNBL), Kainan, Wakayama 642-0017, Japan.
J Vet Med Sci. 2010 Feb;72(2):225-8. doi: 10.1292/jvms.09-0341. Epub 2009 Nov 25.
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.
由于猕猴在进化上与人类接近，因此被广泛用于药物代谢研究。然而，药物代谢酶的遗传背景尚未得到充分研究；因此，鉴定和表征药物代谢酶基因对于理解该物种的药物代谢很重要。在本研究中，我们在食蟹猴中分离并表征了一种新型细胞色素P450 2C18（CYP2C18）cDNA。该cDNA与人CYP2C18 cDNA高度同源（96%）。食蟹猴CYP2C18在肝脏和肾脏中优先表达。此外，使用在大肠杆菌中异源表达的食蟹猴CYP2C18蛋白进行的代谢试验显示了其对S-美芬妥因4'-羟基化的活性。这些结果表明，食蟹猴CYP2C18可能在肝脏中作为药物代谢酶发挥作用。
