Volkova_1976_Biokhimiia_41_443

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.