Acetylcholine

• Acetylcholine (ACh) is a neurotransmitter a chemical messenger that plays a crucial role in transmitting signals in both the central and peripheral nervous systems.

Biosynthesis of acetylcholine

1. Location

   • Synthesized in the cytoplasm of cholinergic neurons, particularly at nerve terminals.

2. Precursors

   • Choline: Obtained from diet and recycled ACh.
   • Acetyl-CoA: Formed in mitochondria from pyruvate (product of glucose metabolism).

3. Enzyme Involved

   • Choline acetyltransferase (ChAT): Exclusively present in cholinergic neurons.

Step-by-Step Process

1. Uptake of Choline

   • Choline enters the presynaptic neuron via high-affinity choline transporters (CHT1).
   • This is an active, sodium-dependent
   • Choline can be derived from:
   • Diet (e.g., eggs, meat)
   • Breakdown of previously released acetylcholine

2. Production of Acetyl-CoA

   • Produced by the pyruvate dehydrogenase complex in mitochondria.
   • Acetyl-CoA provides the acetyl group for ACh synthesis.

3. Synthesis of Acetylcholine

   • Catalyzed by choline acetyltransferase (ChAT) in the cytoplasm.
   • Reaction:
   • $\mathrm{Choline + Acetyl\text{-}CoA \longrightarrow Acetylcholine + CoA}
     $

4. Storage in Vesicles

   • It is actively transported into synaptic vesicles by vesicular acetylcholine transporter (VAChT).
   • Stored until released upon nerve stimulation.

5. Release

   • Triggered by influx of calcium ions following an action potential.
   • Vesicles fuse with the presynaptic membrane and release ACh via exocytosis.

Catabolism of acetylcholine

1. Enzyme Involved

   • Acetylcholinesterase (AChE): Present in the synaptic cleft and on postsynaptic membranes.

2. Reaction

   • $\text{Acetylcholine} \longrightarrow \text{Choline} + \text{Acetate}
     $
   • Choline: Taken back up by presynaptic choline transporters and reused.
   • Acetate: Diffuses away and is metabolized.

3. Importance

   • Prevents continuous stimulation of the postsynaptic cell.
   • Ensures precise, short-lived synaptic signaling.
   • Rapid breakdown (within milliseconds) is crucial, especially at neuromuscular junctions.

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