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Home / Drug Metabolism Letters, Volume 3, Number 4

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

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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: CYP3A43; cloning; cytochrome P450; liver; macaque

Document Type: Research Article

Publication date: 01 December 2009

More about this publication?
  • Drug Metabolism Letters publishes short papers on major advances in all areas of drug metabolism and disposition. The emphasis will be on publishing quality papers very rapidly. Letters will be processed rapidly by taking full advantage of the Internet technology for both the submission and review of manuscripts. The journal covers the following areas:

    In vitro systems including CYP-450; enzyme induction and inhibition; drug-drug interactions and enzyme kinetics; pharmacokinetics, toxicokinetics, species scaling and extrapolations; P-glycoprotein and transport carriers; target organ toxicity and interindividual variability; drug metabolism and disposition studies; extrahepatic metabolism; phase I and phase II metabolism; recent developments for the identification of drug metabolites, reactive intermediate and glutathione conjugates.
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