A Density-Functional Study of the Conformational Preference of Acetylcholine in the Neutral Hydrolysis.

Rizka N Fadilla,Mudasir Mudasir,Ira Puspitasari,Vera Khoirunisa,Faozan Ahmad,Hermawan K Dipojono,Nufida D Aisyah,Febdian Rusydi

doi:10.3390/molecules25030670

Abstract

Acetylcholine, which is associated with Alzheimer’s disease, is widely known to have conformers. The preference of each conformer to undergo neutral hydrolysis is yet to be considered. In this study, we employed density-functional calculations to build the conformers and investigated their preference in one-step neutral hydrolysis. The results showed the preference in ten possible hydrolysis pathways involving seven acetylcholine conformers (reactant), four transition state structures, and two choline conformers (product). Three out of the seven acetylcholine conformers predicted from the results confirmed experimental findings on the conformers stability. We suggested that two out of ten possible pathways were observed in the experimental results based on agreement in reaction energy. Eventually, this study will emphasize the importance of considering acetylcholine conformers in its hydrolysis study.

Highlights

Acetylcholine (ACh+), the organic molecule acting as neurotransmitter in the brain, is associated with the treatment of Alzheimer’s disease (AD) [1]
We have reported that each ACh+ conformer exhibited different conformational preferences when existing as an individual molecule and as an activated [ACh+–water] complex of a neutral hydrolysis
Three out of the five low-level conformers were observed in the experiments

Summary

Introduction

Acetylcholine (ACh+), the organic molecule acting as neurotransmitter in the brain, is associated with the treatment of Alzheimer’s disease (AD) [1]. AD is a progressive brain disease that slowly impairs coordination among neurons and leads to loss of body function [2]. A common explanation for AD is the cholinergic hypothesis, which states the cause as ACh+ depletion [3,4]. ACh+ is to transmit signals among neurons [5], its depletion can disturb the signal transmission in the brain and can lead to loss of body function. One way to treat AD is by reducing the rate of ACh+ neutral hydrolysis [1,6], which decomposes. Because it is important to preserve sufficient ACh+ concentration in the brain of AD patients, reducing the rate of ACh+ neutral hydrolysis becomes an option to compensate for ACh+ depletion

Methods

Results

Conclusion