Acetylcholine is synthesized in nerve terminals from choline and acetyl CoA in a reaction catalyzed by the enzyme choline acetyltransferase (ChAT).
Choline, which is taken up into the neuron by a choline transporter, combines with acetyl CoA, a product of glucose metabolism, in the neuron's cytoplasm.
The enzyme choline acetyltransferase catalyzes the transfer of the acetyl group from acetyl CoA to choline, forming acetylcholine.
The newly synthesized acetylcholine is then packaged into synaptic vesicles by an active transport process involving a vesicular acetylcholine transporter (VAChT).
Storage of Acetylcholine:
Once synthesized, acetylcholine is packaged into vesicles by an active transport process that is driven by a proton gradient across the vesicle membrane.
The vesicular acetylcholine transporter (VAChT) is responsible for this packaging process.
Release of Acetylcholine:
When an action potential reaches the nerve terminal, it triggers the opening of voltage-gated calcium channels. The influx of calcium into the cell triggers the fusion of the acetylcholine-containing vesicles with the cell membrane.
Acetylcholine is then released into the synaptic cleft via exocytosis. It can then bind to and activate postsynaptic acetylcholine receptors on the target cell, leading to a biological response.
After release, the action of acetylcholine is terminated by the enzyme acetylcholinesterase, which is located in the synaptic cleft and breaks down acetylcholine into choline and acetate. The choline can be taken up by the presynaptic neuron and reused to form more acetylcholine, thus completing the cycle.
Catabolism of Acetylcholine:
The breakdown of acetylcholine is accomplished by the enzyme acetylcholinesterase, which is present in the synaptic cleft and on the postsynaptic membrane.
After acetylcholine is released into the synaptic cleft and binds to its receptors, it is rapidly broken down by acetylcholinesterase.
Acetylcholinesterase hydrolyzes acetylcholine into choline and acetate. This reaction is extremely fast, which allows the signal sent by the acetylcholine to be rapidly terminated.
The choline produced by this reaction can be taken up again by the presynaptic neuron via the choline transporter, to be used to synthesize more acetylcholine, thus completing the cycle.
Inhibitors of acetylcholinesterase (like physostigmine, neostigmine, and donepezil) can be used therapeutically to increase the amount of acetylcholine available in the synaptic cleft, and are used in conditions like myasthenia gravis, glaucoma, and Alzheimer's disease.