A quantitative analysis of the kinetics of cholinesterase inhibition in tissue homogenates of mice and houseflies

Abstract

The paper deals with investigations on the inhibition of the cholinesterases in mouse-brain and housefly-head homogenates by O,O-dimethyl O-2,2-dichlorovinyl phosphate (DDVP). Its purpose is to explain the remarkable difference in susceptibility to DDVP between the two preparations. Several aspects of the inhibition process and the participating compounds were studied, such as (a) the relation between the amount of inhibitor used and the percentage inhibition finally obtained, (b) the reversibility of the inhibition process and the rate of reversion, (c) the rate of the inhibitory reaction and the affinity between enzyme and inhibitor, and (d) the binding of DDVP to other compounds, e.g. proteins, present in the homogenates. From the results it is concluded that the difference in susceptibility to DDVP (I50 mouse-brain-ChE = 10−7 M; I50 fly-head-ChE = 10−9 M) is mainly due to three co-operating factors: (1) Inhibition of mouse-brain-ChE by DDVP is slowly reversible, whereas fly-head-ChE is irreversibly inhibited; (2) DDVP has a much greater affinity for fly-head-ChE than for mouse-brain-ChE; (3) The concentration of DDVP is considerably reduced by reversible binding to some compound present in the mouse-brain homogenates.

Horse-serum-ChE also proved to be reversibly inhibited. The paper does not, however, contain quantitative data on this preparation.