Butyrylcholinesterase and Erythrocyte Sulfhydryl-dependent Enzyme Hydrolyze Gabexate in Human Blood

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概要

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• Gabexate (GB), a serine protease inhibitor that is widely used for the treatment of acute pancreatitis and disseminated intravascular coagulation, has been reported to be partly hydrolyzed by human serum albumin. However, other enzymes responsible for GB hydrolysis in human blood remain unclear. In this study, we examined in vitro metabolism of GB with human blood samples. The hydrolytic activities of the plasma and erythrocytes at 100 μM of GB were 167 ± 26 and 151 ± 9 nmol/min/ml blood fraction (mean ± S.D., n = 8), respectively. Kinetic analysis indicated that V_<max> and K_m values were 1.75 μmol/min/ml blood fraction and 529 μM for the plasma and 10.6 μmol/min/ml blood fraction and 7360 μM for the erythrocytes, respectively. The activity of human plasma was inhibited by ethopropazine, a butyrylcholinesterase inhibitor (27% inhibition at 100 μM). Furthermore, the plasma activity was inhibited by 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB) (40% inhibition at 5000 μM), suggesting the involvement of albumin in the plasma GB hydrolysis. The erythrocyte activity was also decreased by DTNB (56% inhibition at 5000 μM), implying that this activity was dependent on the presence of sulfhydryl group(s), while little or no inhibition of the activity was seen with phenylmethylsulfonyl fluoride, diisopropyl fluorophosphate, and BW284C51. Butyrylcholinesterase from human serum showed GB hydrolytic activity with V_<max> of 363 nmol/min/mg protein and K_m of 263 μM. These results suggest that, in addition to albumin, butyrylcholinesterase and erythrocyte sulfhydryl-dependent enzyme are responsible for GB hydrolysis in human blood.

• 社団法人日本薬学会の論文
• 2007-02-01

著者

• YAMAMOTO IKUO

  Department of Laboratory Medicine, Miyazaki Medical College

• 景山 節

  京大・霊長類研・生化学

• Yamamoto Ikuo

  Department Of Hygienic Chemistry School Of Pharmaceutical Sciences Kyushu University Of Health And W

• Matsumura Kenji

  Drug Information Department Torii Pharmaceutical Co. Ltd.

• Yamaori Satoshi

  Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Hokuriku University

• Kushihara Mika

  Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Hokuriku University

• Fujiyama Nobuhiro

  Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Hokuriku University

• Funahashi Tatsuya

  Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Hokuriku University

• Kimura Toshiyuki

  Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Hokuriku University

• Oda Minoru

  Drug Information Department, Torii Pharmaceutical Co., Ltd.

• Watanabe Kazuhito

  Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Hokuriku University

• Oda Minoru

  Drug Information Department Torii Pharmaceutical Co. Ltd.

• Kushihara Mika

  Department Of Hygienic Chemistry Faculty Of Pharmaceutical Sciences Hokuriku University

• YAMAMOTO Ikuo

  School of Pharmaceutical Sciences, Kyushu University of Health and Welfare

• Yamamoto Ikuo

  北陸大学 薬 衛化

• Yamamoto Ikuo

  Department Of Hygienic Chemistry Faculty Of Pharmaceutical Sciences Hokuriku University

• YAMAMOTO IKUO

  Hygienic Chemistry

• Kimura T

  Department Of Hygienic Chemistry Faculty Of Pharmaceutical Sciences Hokuriku University

• 景山 節

  京都大学霊長類研究所人類進化モデル研究センター

• 景山 節

  京大・霊長研

• Yamaori Satoshi

  Department Of Hygienic Chemistry Faculty Of Pharmaceutical Sciences Hokuriku University

• Kimura Toshiyuki

  Department Of Hygienic Chemistry Faculty Of Pharmaceutical Sciences Hokuriku University

• Fujiyama Nobuhiro

  Department Of Hygienic Chemistry Faculty Of Pharmaceutical Sciences Hokuriku University

• Fujiyama Nobuhiro

  Department Of Biopharmaceutics Graduate School Of Pharmaceutical Sciences Chiba University

• Watanabe Kazuhito

  Department Of Hygienic Chemistry Faculty Of Pharmaceutical Sciences Hokuriku University

• Watanabe Kazuhito

  Department Of Chemistry And Chemical Engineering Faculty Of Engineering Yamagata University

• Funahashi Tatsuya

  Department Of Hygienic Chemistry Faculty Of Pharmaceutical Sciences Hokuriku University

• Kimura T

  Department Of Medicinal Chemistry Center For Frontier Research In Medicinal Science 21st Century Coe

• Yamamoto I

  Hokuriku Univ. Kanazawa Jpn

• Yamamoto I

  Hygienic Chemistry

• Watanabe Kazuhito

  Faculty Of Pharmaceutical Sciences Kyushu University

• Yamamoto Ikuo

  Hygienic Chemistry School Of Pharmacy Hokuriku University

• Yamamoto Ikuo

  Department Of Bioapplied Chemistry Faculty Of Engineering Osaka City University

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