title: Systematic identification and characterization of carboxylesterases in cynomolgus macaques.
abstract: Carboxylesterase (CES) is important for detoxification of a wide range of drugs and xenobiotics and catalyzes cholesterol and fatty acid metabolism. Cynomolgus macaques are widely used in drug metabolism studies; however, cynomolgus CES has not been fully investigated at molecular levels, partly due to the lack of gene information. In this study, we isolated and characterized cDNAs for CES homologous to human CES1, CES2, and CES5A in cynomolgus macaques. By genome analysis, in the cynomolgus macaque genome, three gene sequences were found for CES1(v1-3) and CES2(v1-3), whereas one gene sequence was found for CES5A. Cynomolgus CES1, CES2, and CES5A genes were located in the genomic regions corresponding to the human genes. We successfully identified CES1v1, CES1v2, CES2v1, CES2v3, and CES5A cDNAs from cynomolgus liver. Sequence analysis showed that amino acid sequences of each CES were highly homologous to that of the human homolog. All five CESs had sequences characteristic for CES enzymes, including the catalytic triad and oxyanion hole loop. By quantitative polymerase chain reaction, the most abundant expression of CES mRNAs among the 10 tissue types analyzed was observed in liver (CES1v1 and CES2v3 mRNAs), jejunum (CES2v1 mRNAs), and kidney (CES1v2 and CES5A mRNA), the organs important for drug metabolism and excretion. The results indicated that cynomolgus macaques express at least five CES genes, which potentially encode intact CES proteins.
authors.affiliation: Pharmacokinetics and Bioanalysis Center, Shin Nippon Biomedical Laboratories, Kainan, Japan (Y.U., S.U.); Laboratory of Drug Metabolism and Biopharmaceutics, Faculty of Pharmaceutical Sciences, Chiba Institute of Science, Choshi, Japan (M.H.); and Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan (T.I.) uno-yasuhiro@snbl.co.jp.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Uno
authors.affiliation: Pharmacokinetics and Bioanalysis Center, Shin Nippon Biomedical Laboratories, Kainan, Japan (Y.U., S.U.); Laboratory of Drug Metabolism and Biopharmaceutics, Faculty of Pharmaceutical Sciences, Chiba Institute of Science, Choshi, Japan (M.H.); and Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan (T.I.).
authors.forename: Shotaro
authors.initials: S
authors.lastname: Uehara
authors.affiliation: Pharmacokinetics and Bioanalysis Center, Shin Nippon Biomedical Laboratories, Kainan, Japan (Y.U., S.U.); Laboratory of Drug Metabolism and Biopharmaceutics, Faculty of Pharmaceutical Sciences, Chiba Institute of Science, Choshi, Japan (M.H.); and Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan (T.I.).
authors.forename: Masakiyo
authors.initials: M
authors.lastname: Hosokawa
authors.affiliation: Pharmacokinetics and Bioanalysis Center, Shin Nippon Biomedical Laboratories, Kainan, Japan (Y.U., S.U.); Laboratory of Drug Metabolism and Biopharmaceutics, Faculty of Pharmaceutical Sciences, Chiba Institute of Science, Choshi, Japan (M.H.); and Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan (T.I.).
authors.forename: Teruko
authors.initials: T
authors.lastname: Imai
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002265:Carboxylic Ester Hydrolases / Q000235:genetics* / Q000378:metabolism*; D018076:DNA, Complementary / Q000235:genetics; D023281:Genomics / Q000379:methods; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008252:Macaca fascicularis / Q000235:genetics* / Q000378:metabolism*; D010802:Phylogeny; D017386:Sequence Homology, Amino Acid
chemical_list: D018076:DNA, Complementary; D002265:Carboxylic Ester Hydrolases