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AAT Bioquest

What is the mechanism of acetylcholine synthesis?

Posted January 16, 2024


Answer

Acetylcholine is synthesized within nerve terminals. This process involves combining  acetyl CoA with choline in a reaction facilitated by the enzyme choline acetyltransferase (CAT). Within the neuron, both CAT and ACh can be found, but their highest concentration is typically observed in axon terminals. The presence of CAT within a neuron strongly suggests the utilization of acetylcholine as one of its neurotransmitters. The rate-limiting factors influencing ACh synthesis are the availability of choline and acetyl-CoA. Increased neuronal activity induces an upregulation in the availability of acetyl-CoA from mitochondria and enhances the uptake of choline into nerve endings from the synaptic cleft. Calcium ions (Ca2+) are involved in regulating these processes. Upon ACh inactivation, it is metabolized into choline and acetic acid. Choline utilized for ACh synthesis largely comes from the recycling of choline derived from metabolized ACh. Another source of choline is the breakdown of phosphatidylcholine, a phospholipid. One approach to potentially boost ACh neurotransmission involves administering choline in the diet. However, this strategy hasn't been effective, likely because the introduction of choline doesn't significantly increase choline availability within the CNS.

Additional resources

Synthesis, Storage and Release of Acetylcholine

Enzymes

Amplite® Fluorimetric Acetylcholine Assay Kit *Red Fluorescence*