Hydrolysis of Acetylcholine
The enzyme catalyzes a biochemical hydrolysis reaction in 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: Cleavage of the ester bond releases choline ($HO-CH_2-CH_2-N^+(CH_3)_3$) and acetic acid ($CH_3-COOH$).
Thus, the enzyme ensures the inactivation of the neurotransmitter 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 primary role is to electrostatically attract and firmly anchor the substrate. Fixation occurs through interaction with the positively charged quaternary ammonium nitrogen group ($N^+$) of acetylcholine.
- Esterase site (catalytic site). This is where the actual chemical reaction takes place—the hydrolysis of the neurotransmitter's ester bond.
Mechanism of Normal Catalysis
Under normal conditions, the hydrolysis process 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 within the catalytic (esterase) site.
- Chemical cleavage of the substrate occurs with the incorporation of a water molecule.
Competitive Inhibition of the Enzyme
Certain chemical agents can block the action of acetylcholinesterase. Competitive inhibitors occupy the enzyme's active site, preventing the binding of the natural substrate. As a result, acetylcholine is not degraded and begins to accumulate in the synaptic cleft. Such substances include:
- Proserinum (Neostigmine / Proserine). Structurally resembles acetylcholine and contains a positively charged group. By occupying the active site, it physically blocks access for the neurotransmitter.
- Edrophonium. Also interacts with the anionic site of the enzyme. Binding is achieved via the positive charge on the nitrogen atom and a hydroxyl group that mimics the structure of the natural substrate.