神经毒性和非神经毒性有机磷化合物对脑羧酸酯酶的抑制作用。

Inhibition of brain carboxylesterases by neurotoxic and nonneurotoxic organophosphorus compounds.

作者信息

Chemnitius J M, Zech R

出版信息

Mol Pharmacol. 1983 May;23(3):717-23.

Abstract

Carboxylesterases (EC 3.1.1.1) of chicken brain were investigated by applying kinetic analysis of organophosphorus inhibition. By iterative elimination of exponential inhibition curves and by sequential inhibition experiments using a combination of two organophosphorus inhibitors, 11 different carboxylesterases of chicken brain were characterized with respect to their phenyl valerate-hydrolyzing activity (milliunits per gram of brain) and their inhibition by O,O-diethyl O-4-nitrophenyl phosphate (Paraoxon), O,O-diisopropylphosphorofluoridate, and N,N'-diisopropylphosphorodiamidic fluoride (Mipafox). The bimolecular inhibition rate constants (liters . mole-1 . min-1) were calculated for the 11 enzymes and 3 organophosphorus compounds. The corresponding data for acetylcholinesterase (EC 3.1.1.7) in chicken brain were determined. The importance of inhibition rate constants for the development of acute cholinergic symptoms, delayed neurotoxicity, and atypical organophosphate effects is shown.

摘要

通过对有机磷抑制作用进行动力学分析，对鸡脑羧酸酯酶（EC 3.1.1.1）展开了研究。通过迭代消除指数抑制曲线，并使用两种有机磷抑制剂的组合进行顺序抑制实验，对鸡脑的11种不同羧酸酯酶进行了表征，涉及它们水解戊酸苯酯的活性（每克脑的毫单位）以及它们被O,O-二乙基-O-4-硝基苯基磷酸酯（对氧磷）、O,O-二异丙基磷酰氟和N,N'-二异丙基磷酰二胺氟化物（丙胺氟磷）抑制的情况。计算了这11种酶和3种有机磷化合物的双分子抑制速率常数（升·摩尔⁻¹·分钟⁻¹）。测定了鸡脑乙酰胆碱酯酶（EC 3.1.1.7）的相应数据。展示了抑制速率常数在急性胆碱能症状、迟发性神经毒性和非典型有机磷效应发展中的重要性。