Inhibition and protection of cholinesterases by methanol and ethanol

Abstract

The cholinesterases have been investigated in terms of the effects of methanol and ethanol on substrate and carbamate turnover, and on their phosphorylation. It was found: 1) that at low substrate concentrations the two alcohols inhibit all three tested cholinesterases and that the optimum activities are shifted towards higher substrate concentrations, but with a weak effect on horse butyrylcholinesterase; 2) that methanol slows down carbamoylation by eserine and does not influence decarbamoylation of vertebrate and insect acetylcholinesterase and 3) that ethanol decreases the rate of phosphorylation of vertebrate acetylcholinesterase by DFP. Our results are in line with the so-called 'approach-and-exit' hypothesis. By hindering the approach of substrate and the exit of products, methanol and ethanol decrease cholinesterase activity at low substrate concentrations and allow for the substrate inhibition only at higher substrate concentrations. Both effects appears to be a consequence of the lower ability of substrate to substitute alcohol rather than water. It also seems that during substrate turnover in the presence of alcohol the transacetylation is negligible.

Use of connectivity index and simple topological parameters for estimating the inhibition potency of acetylcholinesterase

“…Uncertainty in the IC 50 value determination is caused by the type and concentration of the substrate used for measurements and therefore K i is a more reliable parameter, as it is a measure of enzyme ligand affinity in the absence of a substrate. The negative effect of the solvent mixture on the AChE enzyme activity when using ethanol or DMSO buffer should be tested, as ethanol or DMSO apparently increase the ligand inhibition potency due to AChE inhibition ( Fekonja et al, 2007 , Kumar and Darreh-Shori, 2017 ). Therefore, the effect of a solvent on AChE activity needs to be characterized and compensated properly.…”

Microbial-Driven Synthesis and Hydrolysis of Neohesperidin Dihydrochalcone: Biotransformation Process and Feasibility Investigation

“…Interestingly, two hydrolysis products were still found in the water system before 48 h, but HDC-G eventually disappeared at 48 h. Some studies have reported that methanol had an impairing effect on enzyme activities and that excessive use of methanol may even inactivate the enzyme. This could explain the difference in the conversion of NHDC between the methanol–buffer system and the deionized water–buffer system. , In deionized water, the glucosidase activity can be fully retained and therefore catalyze the hydrolysis of NHDC to produce HDC. However, in the methanol–buffer system, methanol partially inhibited the activity of glucosidase in whole-cell catalysts, thus preventing the complete synthesis of HDC.…”

“…This could explain the difference in the conversion of NHDC between the methanol−buffer system and the deionized water−buffer system. 31,32 In deionized water, the glucosidase activity can be fully retained and therefore catalyze the hydrolysis of NHDC to produce HDC. However, in the methanol−buffer system, methanol partially inhibited the activity of glucosidase in whole-cell catalysts, thus preventing the complete synthesis of HDC.…”

Evidence for Subdomain Flexibility in Drosophila melanogaster Acetylcholinesterase

“…The experiments in the presence of different reversible inhibitors were performed under the same conditions as the control experiments without them. Scheme and the corresponding equation (see the expression for A in the Appendix, and ref ) were used to describe the dependence of initial enzyme activity at different substrate concentrations (pS curves) in the absence and presence of inhibitors. Hydrolysis of o -nitrophenyl acetate in 25 mM phosphate buffer (pH 7) and 5% DMSO was monitored by the formation of o -nitrophenolate at 405 nm, with the Michaelis−Menten equation used for the analysis.…”