## Acetylcholine Hydrolysis by Acetylcholinesterase **Key Point:** Acetylcholinesterase (AChE) catalyzes the rapid hydrolysis of acetylcholine (ACh) into **acetic acid** and **choline** via ester bond cleavage. ### Reaction Mechanism **Acetylcholine → Acetic Acid + Choline** The enzyme cleaves the ester linkage between the acetyl group and choline: - **Substrate:** CH₃-CO-O-CH₂-CH₂-N⁺(CH₃)₃ (acetylcholine) - **Products:** CH₃-COOH (acetic acid) + HO-CH₂-CH₂-N⁺(CH₃)₃ (choline) ### Clinical Significance **High-Yield:** This is the rate-limiting step in cholinergic neurotransmission termination. Inhibition of AChE by drugs (physostigmine, neostigmine, organophosphates) leads to accumulation of ACh and prolonged receptor activation. **Mnemonic:** **ACh → AA + C** — **A**cetylcholine yields **A**cetic acid and **C**holine. ### Recycling of Choline The choline produced is recycled back into the presynaptic neuron via the **high-affinity choline transporter (CHT1)** and re-acetylated by **choline acetyltransferase (ChAT)** to regenerate acetylcholine. **Clinical Pearl:** Choline availability is rate-limiting for ACh synthesis in some conditions. Dietary choline supplementation or drugs that enhance choline uptake may improve cholinergic function in certain neurodegenerative diseases.
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