Volkova R I, Dmitrieva E N
Biokhimiia. 1976 Mar;41(3):443-51.
Reversible inhibition of acetylcholinesterase (AChE) from bovine erythrocytes and butyrylcholinesterase (BuChE) from horse blood serum by quaternary diaminoalkyl esters of suberic (D-6), p-phenylenediacetic (PK-139), p-phenylenedipropionic (PK-154 and PK-155), p-phenylenediacrylic (PK-150 and PK-151) and phthalic (PK-105) acids, was studied under the following incubation conditions: pH 7.5, 25 degrees C, 0.1 M KCl. The inhibition kinetics were of a mixed competitive-incompetitive type, the incompetitive component alpha'-having higher values for AChE (0.26-0.60) than for BuChE (0.10-0.20). Diester PK-150 selectively inhibited BuChE (Ki=3.0-10(-6) M); its Ki value for AChE was 4.0-10(-4) M. The other diesters had a stronger inhibitory effect on AChE than on BuChE. High values of alpha' observed during AChE inhibition cannot be interpreted in terms of interaction of those bisquaternary compounds with the anionic site of the acetylated active centre and are probably due to their sorbtion at the peripheral anionic sites. Incompetitive inhibition constants (K'i=Ki/alpha') of BuChE by the diesters PK-139, PK-154 and PK-150 were found to be values of the same order as substrate inhibition constants determined in the course of BuChE hydrolysis of these diesters. Incompetitive inhibition found for the esters studied and substrate inhibition during hydrolysis of these compounds are presumably due to the same mechanism.
pH 7.5、25℃、0.1M KCl，研究了辛二酸（D - 6）、对苯二甲酸（PK - 139）、对苯二甲酸二丙酸酯（PK - 154和PK - 155）、对苯二甲酸二丙烯酸酯（PK - 150和PK - 151）以及邻苯二甲酸（PK - 105）的季铵二氨基烷基酯对牛红细胞乙酰胆碱酯酶（AChE）和马血清丁酰胆碱酯酶（BuChE）的可逆抑制作用。抑制动力学为混合竞争性 - 非竞争性类型，非竞争性组分α'在AChE中的值（0.26 - 0.60）高于在BuChE中的值（0.10 - 0.20）。二酯PK - 150选择性抑制BuChE（Ki = 3.0×10⁻⁶ M）；其对AChE的Ki值为4.0×10⁻⁴ M。其他二酯对AChE的抑制作用比对BuChE更强。在AChE抑制过程中观察到的高α'值不能用这些双季铵化合物与乙酰化活性中心阴离子位点的相互作用来解释，可能是由于它们在外周阴离子位点的吸附。发现二酯PK - 139、PK - 154和PK - 150对BuChE的非竞争性抑制常数（K'i = Ki/α'）与在这些二酯的BuChE水解过程中测定的底物抑制常数处于同一数量级。所研究酯类的非竞争性抑制以及这些化合物水解过程中的底物抑制可能是由于相同的机制。
