@article{oai:gifu-pu.repo.nii.ac.jp:00012165,
 author = {杉山, 正 and 片桐, 義博 and 臼井, 茂之 and 平野, 和行 and スギヤマ, タダシ and カタギリ, ヨシヒロ and ウスイ, シゲユキ and ヒラノ, カズユキ and SUGIYAMA, Tadashi and KATAGIRI, Yoshihiro and USUI, Shigeyuki and HIRANO, Kazuyuki},
 journal = {岐阜藥科大學紀要, The annual proceedings of Gifu College of Pharmacy},
 month = {Jun},
 note = {P(論文), ラット,ブタ,ヒトの肝臓からカルボキシルェステラーゼを精製し,その基質特異性などの諸性質を検討した。ラットからはcarboxylesterase pI 6.0とcarboxylesterase pI 6.2,ブタからはインドメタシン水解酵素,ヒトからはcarboxylesterase pI 5.3とcarboxylesterase pI 4.5を得た。これらの酵素のうちラット由来のcarboxylesterase pI 6.2のみがプランルカストに対して水解活性を示し,この基質特異性の差がヒトとラットでのプランルカストの代謝経路の違いの原因であると考えられた。プタ由来のインドメタシン水解酵素は,カルボキシルエステラーゼの一般的な基質であるα-naphthyl acetate に対して水解活性を示さず,アミノ酸配列の解析から新規の酵素であると考えられた。ヒト由来の2種類のカルボキシルエステラーゼの基質特異性は大きく異なっていた。これらの結果は,カルボキシルエステラーゼの種差および基質特異性の情報はエステル型およびアミド型薬物の代謝を理解する上で重要であることを示している。なお,本研究では基質特異性の検討を簡便かつ短時間に行うためにHPLCでの移動相の簡便な選択法の開発を行った。, Carboxylesterases designated as carboxylesterase pI 6.0 and pI 6.2,indomethacin hydrolyzing enzyme, and carboxylesterase pI 5.3 and pI 4.5 from the livers of rat, pig, and human, respectively, were purified to electrophoretic homogeneity by several stages of column chromatography. Some properties, especially the substrate specificity, of these esterases were clarified. Pranlukast was effectively hydrolyzed by carboxylesterase pI 6.2 from rat but not by another esterases, suggesting that the substrate specificity of carboxylesterases from rat and human reflects the difference in pranlukast metabolism between the two species. Indomethacin hydrolyzing enzyme from pig exhibited no catalytic activity for α-naphthylacetate, which is a typical substrate of carboxylesterases. Amino acid sequence analysis of this hydrolyzing enzyme revealed it to be a novel esterase. The substrate specificity of carboxylesterase pI 5.3 and pI 4.5 from human was observed to be quite different. These results imply that the differences in the substrate specificity of carboxylesterases between specics is helpful to understand the metabolism of ester- and amide-type drugs. In this study, a convenient method was developed to select the mobile phase to separate drugs commonly used in clinical therapy, using high-performance liquid chromatography (HPLC) , and applied to assay for the substrate specificity of carboxylesterases. Using this method, the time required for not only the setting of HPLC conditions, but also the analysis was shortened.},
 pages = {25--36},
 title = {<総説>肝臓由来の薬物水解酵素の精製と諸性質の検討},
 volume = {50},
 year = {2001},
 yomi = {スギヤマ, タダシ and カダギリ, ヨシヒロ and ウスイ, シゲユキ and ヒラノ, カズユキ}
}