Characterization of cynomolgus monkey cytochrome P450 (CYP) cDNAs:: Is CYP2C76 the only monkey-specific CYP gene responsible for species differences in drug metabolism?

被引：63
作者：
Uno, Yasuhiro
Hosaka, Shinya
Matsuno, Kiyomi
Nakamura, Chika
Kito, Go
Kamataki, Tetsuya
Nagata, Ryolchl
机构：
[1] Shin Nippon Biomed Labs SNBL Ltd, Pharmacokinet & Bioanal Ctr PBC, Kainan 6420017, Japan
[2] Hokkaido Univ, Grad Sch Pharmaceut Sci, Lab Translat Res, Kita Ku, Sapporo, Hokkaido 0600812, Japan
[3] Shin Nippon Biomed Labs SNBL Ltd, Drug Safety Res Labs DSR, Kagoshima 8911394, Japan
[4] Hokkaido Univ, Grad Sch Pharmaceut Sci, Lab Drug Metab, Kita Ku, Sapporo, Hokkaido 060, Japan
来源：
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS | 2007年 / 466卷 / 01期
关键词：
cynomolgus monkey; CYP2A; CYP2C76; CYP2E; CYP2J; CYP3A; CYP4A; CYP4F; drug-metabolizing capability; tissue expression pattern;
D O I：
10.1016/j.abb.2007.07.003
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
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, CYP4173, 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 I I monkey CYP cDNAs are closely related to the human CYP cDNAs and thus, unlike CYP2C76, are not apparent monkey-specific cDNAs. (c) 2007 Elsevier Inc. All rights reserved.
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页码：98 / 105
页数：8
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