Drug Metabolism Letters

Zhiyang Zhao
Amgen
Cambridge, MA
USA

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Cloning, Expression, and Characterization of CYP3A43 in Cynomolgus Macaque (Macaca fascicularis)

Author(s): Yasuhiro Uno, Kiyomi Matsuno, Chika Nakamura, Masahiro Utoh, Hiroshi Yamazaki.

Abstract:

Cynomolgus macaques are frequently used in drug metabolism studies due to their evolutionary closeness to humans. Despite their importance, genes encoding drug-metabolizing enzymes have not been fully identified in this species. In this study, the cDNA orthologous to human cytochrome P450 3A43 (CYP3A43) was isolated. The deduced amino acid sequence of this cDNA had a high sequence identity (∼95%) to human CYP3A43 cDNA and contained characteristic motifs for CYP3A proteins, a heme-binding region and substrate recognition sites. Of the 10 tissues analyzed, cynomolgus CYP3A43 was expressed in liver, adrenal gland, and lung, with the highest expression being in liver. Cynomolgus CYP3A43 protein heterologously expressed in Escherichia coli catalyzed the 1-hydroxylation of midazolam. These results indicate that cynomolgus CYP3A43 is expressed in liver and encodes a functional drug-metabolizing enzyme and could play a role in hepatic drug metabolism.

Keywords: macaque, cytochrome P450, CYP3A43, cloning, liver

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Article Details

VOLUME: 3
ISSUE: 4
Year: 2009
Page: [228 - 233]
Pages: 6
DOI: 10.2174/187231209790218127
Price: $58