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Related Concept Videos

Cholinesterases: Distribution and Function01:22

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 Action01:18

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, leading to...
Indirect-Acting Cholinergic Agonists: Chemistry and Structure-Activity Relationship01:29

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: Chemistry and Structure-Activity Relationship01:22

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

Cholinergic agonists or cholinomimetics mimic the action of acetylcholine to stimulate the parasympathetic nervous system. They are categorized into direct-acting and indirect-acting agents. The direct-acting cholinergic drugs induce the parasympathetic response by directly binding to the muscarinic or nicotine receptors. In comparison, the indirect-acting cholinergic drugs prevent acetylcholine hydrolysis, indirectly contributing to the extended parasympathetic response.
The direct-acting...
Cholinergic Neurons: Neurotransmission01:23

Cholinergic Neurons: Neurotransmission

Cholinergic neurotransmission involves the synthesis and the release of acetylcholine (ACh) in order to transmit nerve impulses across the synapse. The process begins with the synthesis of acetyl CoA, a precursor for ACh, from ATP, acetate, and coenzyme A in the mitochondria. Choline, another vital precursor, is transported inside the neuron through choline transporters, including high-affinity choline transporter CHT1, low-affinity choline transporter CTL1, and lower-affinity choline...
Anticholinesterase Agents: Poisoning and Treatment01:26

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 slower than the...

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Related Experiment Video

Updated: Jul 4, 2026

Cholinergic Ligand–dependent Modulation of Oxidative Phosphorylation Coupling in Digitonin-permeabilized BE(2)-C Neuroblastoma Cells
14:39

Cholinergic Ligand–dependent Modulation of Oxidative Phosphorylation Coupling in Digitonin-permeabilized BE(2)-C Neuroblastoma Cells

Published on: April 28, 2026

Acetylcholinesterase: how is structure related to function?

Israel Silman1, Joel L Sussman

  • 1Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.

Chemico-Biological Interactions
|July 1, 2008
PubMed
Summary
This summary is machine-generated.

Acetylcholinesterase, a key enzyme in neurotransmission, features a unique gorge-like active site. This structure is crucial for its high efficiency in acetylcholine hydrolysis and regulating substrate access.

More Related Videos

Direct Detection of the Acetate-forming Activity of the Enzyme Acetate Kinase
05:51

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

Published on: December 19, 2011

Related Experiment Videos

Last Updated: Jul 4, 2026

Cholinergic Ligand–dependent Modulation of Oxidative Phosphorylation Coupling in Digitonin-permeabilized BE(2)-C Neuroblastoma Cells
14:39

Cholinergic Ligand–dependent Modulation of Oxidative Phosphorylation Coupling in Digitonin-permeabilized BE(2)-C Neuroblastoma Cells

Published on: April 28, 2026

Direct Detection of the Acetate-forming Activity of the Enzyme Acetate Kinase
05:51

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

Published on: December 19, 2011

Area of Science:

  • Biochemistry
  • Neuroscience
  • Enzymology

Background:

  • Acetylcholinesterase (AChE) terminates neurotransmission at cholinergic synapses by hydrolyzing acetylcholine.
  • AChE is recognized as one of nature's most efficient enzymes.
  • Its biological role necessitates rapid and precise regulation of acetylcholine levels.

Purpose of the Study:

  • To review the specialized structure of acetylcholinesterase.
  • To examine how its active site architecture contributes to catalytic efficacy.
  • To discuss the mechanisms controlling substrate and product transport to and from the active site.

Main Methods:

  • Structural biology analysis of acetylcholinesterase.
  • Review of existing literature on enzyme kinetics and function.
  • Biochemical and biophysical studies on enzyme-substrate interactions.

Main Results:

  • The three-dimensional structure of AChE reveals an active site at the bottom of a deep, narrow gorge.
  • This sequestered active site architecture was unexpected given the enzyme's high turnover rate.
  • The gorge structure plays a critical role in AChE's catalytic efficiency and substrate specificity.

Conclusions:

  • The unique gorge structure of acetylcholinesterase is essential for its function.
  • This architecture facilitates efficient substrate binding and hydrolysis while preventing unwanted reactions.
  • Understanding AChE's structure provides insights into enzyme catalysis and synaptic regulation.