牛视网膜乙酰胆碱酯酶（E.C. 3.1.1.7）对他克林的敏感性：动力学特征

Sensitivity of bovine retinal acetylcholinesterase (E.C. 3.1.1.7) toward tacrine: kinetic characterization.

作者信息

al-Jafari A A, Kamal M A, Alhomida A S

机构信息

Department of Biochemistry, College of Science, King Saud University, Riyadh, Saudi Arabia.

出版信息

J Biochem Mol Toxicol. 1998;12(4):245-51. doi: 10.1002/(sici)1099-0461(1998)12:4<245::aid-jbt7>3.0.co;2-l.

DOI:10.1002/(sici)1099-0461(1998)12:4<245::aid-jbt7>3.0.co;2-l

PMID:9580877

Abstract

This work addresses the kinetic analysis of the interaction of tacrine with bovine retina acetylcholinesterase (A ChE, E.C. 3.1.1.7). It was found that the tacrine effect was reversible in nature. Tacrine inhibited bovine retinal AChE activity in a concentration-dependent manner; IC50 was fo to be 8.07 nM. The Michaelis-Menten constant (Ka) for the hydrolysis of acetylthiocholine iodide (ASCh) by AChE was 0.061 mM in the control system, and this value was increased by 54-67% in the tacrine-treated systems. The Vmax was 0.701 mumole/min per milligram protein for the control system, but it was decreased by 26-69% in the tacrine-treated systems. The Lineweaver-Burk plot, Dixon plot, and their secondary replots indicated that the nature of the inhibition was of the partial mixed type, that is, a mixture of competitive and noncompetitive inhibition. The values of Ki and Kt were estimated to be as 4.475 and 8.517 nM, respectively.

摘要

这项工作涉及他克林与牛视网膜乙酰胆碱酯酶（A ChE，E.C. 3.1.1.7）相互作用的动力学分析。结果发现，他克林的作用本质上是可逆的。他克林以浓度依赖性方式抑制牛视网膜AChE活性；IC50为8.07 nM。在对照体系中，AChE水解碘化硫代乙酰胆碱（ASCh）的米氏常数（Ka）为0.061 mM，在他克林处理的体系中该值增加了54 - 67%。对照体系的Vmax为每毫克蛋白质0.701微摩尔/分钟，但在他克林处理的体系中降低了26 - 69%。Lineweaver - Burk图、Dixon图及其二次重绘图表明抑制性质为部分混合型，即竞争性抑制和非竞争性抑制的混合物。Ki和Kt值分别估计为4.475和8.517 nM。