Enzyme Kinetics of Norisoboldine Glucuronidation in Rat Liver Microsomes

CHEN Jian-zhong; CHOU Gui-xin; WANG Chang-hong; WANG Zheng-tao

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Enzyme Kinetics of Norisoboldine Glucuronidation in Rat Liver Microsomes

更新时间：2024-01-04

- Enzyme Kinetics of Norisoboldine Glucuronidation in Rat Liver Microsomes
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 18, Issue 21, Pages: 149-153(2012)
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- Published：2012
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CHEN Jian-zhong, CHOU Gui-xin, WANG Chang-hong, et al. Enzyme Kinetics of Norisoboldine Glucuronidation in Rat Liver Microsomes[J]. Chinese journal of experimental traditional medical formulae, 2012, 18(21): 149-153.
DOI：

CHEN Jian-zhong, CHOU Gui-xin, WANG Chang-hong, et al. Enzyme Kinetics of Norisoboldine Glucuronidation in Rat Liver Microsomes[J]. Chinese journal of experimental traditional medical formulae, 2012, 18(21): 149-153. DOI：

摘要

目的: 研究去甲异波尔定在大鼠肝微粒体中的葡萄糖醛酸化酶促反应动力学。方法: 优化去甲异波尔定与大鼠肝微粒体的反应体系

采用超高效液相色谱-质谱联用技术定量检测孵育体系中去甲波尔定代谢产物去甲异波尔定-9-O-α-葡萄糖醛酸苷的浓度

并应用Linewearve-Burk作图分析数据

计算酶促动力学常数。结果: 去甲异波尔定-9-O-α-葡萄糖醛酸苷的酶促反应动力学参数Km 40.7 μmol ·L-1

Vmax=909.1 pmol ·(min ·mg pro)-1

肝清除率CLint(Vmax/Km)=22.3 μL ·min-1 ·mg-1。结论: 该方法简单、快速、可靠

适应于去甲异波尔定的葡萄糖醛酸化代谢研究;葡萄糖醛酸化是去甲异波尔定代谢的重要途径之一

提示葡萄糖醛酸转移酶的基因多态性及相关性的药物相互作用引起的去甲异波尔定活性和毒性作用的变化值得进一步关注。

Abstract

Objective: To investigate the enzyme kinetics of norisoboldine glucuronidation in rat liver microsomes. Method: An UPLC-MS method was developed for determination of norisoboldine-9-O-α-glucuronide

a major metabolite of norisoboldine

in liver microsomes incubation system with sinomenine as internal standard. An optimum incubation system was found and the enzyme kinetics parameters of norisoboldine-9-O-α-glucuronide were analyzed and calculated with Linewearve-Burk graphic method. Result: The Km

Vmax and CLint(Vmax/Km)of norisoboldine-9-O-α-glucuronide were 40.7 μmol·L-1

909.1 pmol·(min·mg pro)-1 and 22.3 μL·min-1·mg-1

respectively. Conclusion: This method is simple

specific and reliable

which is suitable for the in vitro research of norisoboldine glucuronidation.

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Related Institution

School of Chinese Materia Medica， Beijing University of Chinese Medicine

Institute of Information on Traditional Chinese Medicine，China Academy of Chinese Medical Sciences

School of Pharmacy，Nanjing University of Chinese Medicine

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School of Chinese Materia Medica, Beijing University of Chinese Medicine

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