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Cholinesterases: Distribution and Function

Cholinesterases: Distribution and Function

Cholinesterases are a group of serine hydrolase enzymes that play a crucial role in the breakdown of choline esters. The two primary types of cholinesterases are acetylcholinesterases (AChEs) and butyrylcholinesterase (BuChEs), which differ in their distribution, function, and substrate specificity. AChEs, also known as true cholinesterases, specifically hydrolyze acetylcholine, while BuChEs, often referred to as pseudocholinesterases, can hydrolyze various choline esters, including...

Indirect-Acting Cholinergic Agonists: Mechanism of Action

Indirect-Acting Cholinergic Agonists: Mechanism of Action

Indirect-acting cholinergic agonists work by interacting with an enzyme called acetylcholinesterase (AChE) in the synaptic cleft. They can be reversible or irreversible inhibitors and have different effects on the enzyme.
Reversible inhibitors like edrophonium bind to a specific part of the enzyme called the anionic catalytic site. They form noncovalent bonds, which means they are not strongly attached to the enzyme. This creates a temporary and less stable enzyme–inhibitor complex,...

Indirect-Acting Cholinergic Agonists: Chemistry and Structure-Activity Relationship

Indirect-Acting Cholinergic Agonists: Chemistry and Structure-Activity Relationship

Indirect-acting cholinergic agonists are agents that interact with the acetylcholinesterase enzyme in the synaptic cleft, preventing the breakdown of acetylcholine into choline and acetate. Consequently, the concentration of acetylcholine in the synaptic cleft increases. These agonists can be classified into reversible and irreversible inhibitors based on their duration of action.
Reversible inhibitors display short to medium durations of action. Short-acting agents include simple alcohols with...

Direct-Acting Cholinergic Agonists: Pharmacokinetics

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Direct-acting cholinergic agonists, such as synthetic choline esters and naturally occurring alkaloids, exert their effects by enhancing the actions of acetylcholine and stimulating the parasympathetic nervous system. Synthetic choline esters share structural similarities with acetylcholine. For example, they have a positively charged quaternary ammonium or onium group, contributing to their hydrophilic characteristics. As a result, they are poorly absorbed in the body through oral...

Indirect-Acting Cholinergic Agonists: Pharmacological Actions

Indirect-Acting Cholinergic Agonists: Pharmacological Actions

Indirect-acting cholinergic agonists, also known as anticholinesterases, exert their pharmacological effects by enhancing cholinergic transmission in various body parts, including the neuromuscular junction, autonomic cholinergic synapses, and the brain.
At the neuromuscular junction, these agents work by inhibiting the breakdown of acetylcholine, allowing it to remain bound to the receptor and bind to nearby receptors. This process leads to repetitive firing of the endplate, causing muscle...

Anticholinesterase Agents: Poisoning and Treatment

Anticholinesterase Agents: Poisoning and Treatment

Anticholinesterases, also known as cholinesterase inhibitors, work by blocking the breakdown of acetylcholine, leading to its accumulation in the synaptic cleft. This accumulation indirectly enhances both muscarinic and nicotinic actions. These agents are classified as reversible or irreversible based on their mechanism of action.
Irreversible agents form a strong bond with the cholinesterase enzyme, making it inactive. The breakdown of the phosphorylated enzyme is...

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Updated: Feb 24, 2026

Direct Detection of the Acetate-forming Activity of the Enzyme Acetate Kinase

Direct Detection of the Acetate-forming Activity of the Enzyme Acetate Kinase

Published on: December 19, 2011

Computational Studies on Acetylcholinesterases.

Yechun Xu¹, Shanmei Cheng², Joel L Sussman^3,4

¹CAS Key Laboratory of Receptor Research, Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences (CAS), Shanghai 201203, China. ycxu@simm.ac.cn.

Molecules (Basel, Switzerland)

|August 11, 2017

Summary

This summary is machine-generated.

Computational studies reveal that the enzyme acetylcholinesterase

Keywords:

acetylcholinesterase active-site gorge catalytic reaction mechanism computational modeling and simulation ligand trafficking oligomer

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Area of Science:

Biochemistry
Computational Biology
Enzymology

Background:

Enzyme function is modulated by structural dynamics.
Acetylcholinesterase (AChE) exhibits rapid catalysis near the diffusion-controlled limit.
Understanding AChE dynamics is crucial for drug development.

Purpose of the Study:

To provide a comprehensive overview of computational studies on acetylcholinesterase dynamics.
To link enzyme structure, dynamics, and function.
To promote the design of novel AChE inhibitors.

Main Methods:

Computational modeling and simulation techniques.
Analysis of dynamical and conformational properties at the atomic level.
Exploration of enzyme microstates and conformational ensembles.

Main Results:

Computational methods offer atomic-level insights into biomolecular motions.
Studies expand the view of AChE from a single structure to ensembles.
Dynamics are integrated with structure and function for a deeper understanding.

Conclusions:

Computational approaches significantly advance the understanding of enzyme mechanisms.
The dynamics of acetylcholinesterase are key to its function.
This work facilitates structure-based and mechanism-based inhibitor design.