Hydrolysis of acetylcholine
The enzyme catalyzes the biochemical hydrolysis reaction, during which a molecule of acetylcholine interacts with water and breaks down into two components.
- Substrate: Acetylcholine. Its chemical structure is $CH_3-CO-O-CH_2-CH_2-N^+(CH_3)_3$.
- Reaction products: As a result of the cleavage of the ester bond, choline ($HO-CH_2-CH_2-N^+(CH_3)_3$) and acetic acid ($CH_3-COOH$) are released.
Thus, the enzyme ensures the inactivation of the mediator immediately after it has fulfilled its signaling function.
Structure of the active site
For the substrate molecule to bind to the enzyme and undergo chemical transformation, the active site of acetylcholinesterase has a strictly specific structure. It includes two key functional regions:
- Anionic site (binding site). This region carries a negative charge ($\Theta$). Its main task is to electrostatically attract and rigidly fix the substrate. Fixation occurs through interaction with the positively charged quaternary ammonium nitrogen group ($N^+$) that is part of acetylcholine.
- Esteratic site (catalytic region). This is where the chemical reaction itself takes place—the hydrolysis of the ester bond of the mediator molecule.
Mechanism of normal catalysis
The hydrolysis process under normal conditions proceeds in several stages determined by the spatial orientation of the substrate:
- The acetylcholine molecule approaches the active site of the enzyme.
- The positively charged nitrogen atom in the substrate structure binds to the negatively charged anionic site.
- The ester bond of the molecule is precisely positioned in the catalytic (esteratic) site.
- Chemical cleavage of the substrate occurs with the addition of a water molecule.
Competitive enzyme inhibition
Some chemical substances are capable of blocking the work of acetylcholinesterase. Competitive inhibitors occupy the active site of the enzyme, making the attachment of the natural substrate impossible. As a result, acetylcholine is not degraded and begins to accumulate in the synaptic cleft. Such substances include:
- Proserinum (Neostigmine). Structurally resembles acetylcholine and contains a positively charged group. By occupying the active site, it physically blocks access for the mediator.
- Edrophonium (Edrophonium). It also interacts with the anionic site of the enzyme. Binding is ensured due to the positive charge on the nitrogen atom and the hydroxyl group, which mimics the structure of the natural substrate.
Briefly: answers to topical questions
Which amino acid residues form the esteratic (catalytic) center of acetylcholinesterase?
The esteratic (catalytic) center of acetylcholinesterase is formed by the radicals of three amino acids making up the "catalytic triad". The human AChE catalytic center includes:
- Serine (Ser-203) — hydroxyl group;
- Histidine (His-447) — imidazole ring;
- Glutamate (Glu-334) — carboxyl group.
To which class of enzymes according to the international classification does acetylcholinesterase belong?
Acetylcholinesterase belongs to class 3 — Hydrolases, subclass of esterases. These are enzymes that cleave covalent bonds in esters with the addition of a water molecule.
The systematic name of acetylcholinesterase is acetylcholine acylhydrolase.
Where exactly is acetylcholinesterase localized in the neuromuscular synapse?
The sources indicate that acetylcholinesterase is localized in synapses and degrades acetylcholine in the synaptic cleft. However, the exact position of the enzyme relative to the pre- and postsynaptic membrane in the neuromuscular synapse is not detailed in the presented materials.
What substances are irreversible inhibitors of acetylcholinesterase?
Irreversible inhibitors of acetylcholinesterase are organophosphorus compounds (OPCs). They interact with the esteratic center of the enzyme, forming a covalent bond between the phosphoryl residue and the OH group of serine.
As an example of a substance that enters into an irreversible inhibition reaction with acetylcholinesterase, diisopropyl fluorophosphate is mentioned.
What is the difference between true acetylcholinesterase and butyrylcholinesterase (pseudocholinesterase)?
The differences between true acetylcholinesterase and butyrylcholinesterase (pseudocholinesterase) lie in their localization and function:
| Characteristic | Acetylcholinesterase | Butyrylcholinesterase |
|---|---|---|
| Localization | In synapses | Blood plasma, liver, other organs |
| Function | Provides rapid inactivation of the mediator | Hydrolyzes acetylcholine extrasynaptically |
The anionic center of the enzyme attracts nitrogen (A-A), while the esteratic (catalytic) center cleaves the ester bond (E-E).
Class and exam questions
What breakdown products are formed from acetylcholine?
During hydrolysis under the action of acetylcholinesterase, choline and acetic acid are formed.
Due to what does the substrate fixate in the active site?
The positively charged quaternary ammonium nitrogen group in the acetylcholine molecule is attracted to the negatively charged anionic center of the enzyme.
What does the action of neostigmine and edrophonium lead to?
These substances are competitive inhibitors. They block the active site of the enzyme, preventing acetylcholine from being hydrolyzed and causing it to accumulate in the synaptic cleft.
What else to study on this topic
- Chemical structure of acetylcholine
- Mechanisms of formation and cleavage of ester bonds
- Specificity of competitive inhibitors
- Physiological consequences of mediator accumulation in the synaptic cleft
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