基于多衰减曲线计算药物代谢酶动力学参数的新方法  

A Novel Approach for Calculating Kinetic Parameters of Drug-Metabolizing Enzymes Based on Multiple Depletion Curves

作　　者：洪英[1] 郭宾[2] 段俊敏[2] 

机构地区：[1]湖南工业大学科技学院,湖南株洲412007 [2]湖南师范大学化学生物学及中药分析教育部重点实验室,湖南长沙410081

出　　处：《湖南工业大学学报》2011年第1期34-39,共6页Journal of Hunan University of Technology

基　　金：国家自然科学基金资助项目(21005027)

摘　　要：针对近年广泛应用于药代筛选的底物消除法,基于药物多衰减曲线,建立了酶促反应的线性化处理方程,提出了线性转换求解酶动力学参数的新方法。测定了9个探针底物在人肝微粒体中代谢的多衰减曲线,通过线性回归同时获得米氏常数Km、最大反应速率Vmax和内在清除率CLint等参数,并与传统的底物消除曲线拟合法进行比较分析,验证了新方法的有效性。多衰减曲线线性作图是一种简便、直观、可靠的数据可视化处理方法。Aiming at the substrate depletion method widely used in multiple drug filtering, establishes a linear equation of enzymatic reaction based on drug decay curve and proposes a new method for linear conversion solution of enzymes kinetic parameters. Determines decay curves of nine probe metabolic reactions in human liver microsomes and obtains by linear regression the Michaelis constant K, maximum velocity of the metabolic reaction Vmax and intrinsic clearance CLint. Comparing with traditional substrate depletion curvilinear fitting method, verifies the effectiveness of the new method. Multi-linear decay curve mapping is a simple, intuitive and reliable data visualization method.

关 键 词：底物消除 药物代谢酶 米氏方程 动力学参数 线性回归 

分 类 号：Q55[生物学—生物化学]