Choline and the synthesis of acetylcholine

acetylcholine synthesis

This crucifix-shaped molecule is choline, a quaternary saturated amine, which is an essential water-soluble nutrient usually found complexed with B-vitamins.

Delicious natural sources are whole eggs and the fatty animal meat. In certain neurons, choline is metabolised into acetylcholine; the extra acetyl group is donated by acetyl-CoA (which draws on the inexhaustible supply of acetate anions which are constantly burned in the citric acid cycle).

The choline acyltransferase enzyme is responsible for catalyzing this process.

It happens in the body of the neuron, and the finished acetylcholine is transported in vesicles via axoplasmic flow.

This acetylcholine is an ester of acetate and choline.

Acetylcholine metabolism back into acetate and choline

acetylcholine metabolism

Once its job in the synapse is done, synaptic acetylcholinesterase breaks it back down into acetate anions and choline.

This hydrolysis takes less than a millisecond.

The acetate goes god knows where (presumably back into Krebs cycle) and the choline is dutifully reabsorbed by its uptake transporters ( of which there are two, one Na+ /Cl- dependent high affinity transporter and another independent transporter of lower affinity).

This reuptake is the rate-limiting step in acetylcholine synthesis.

References

For this sort of really basic stuff, no matter where you look you will find essentially the same information.


I used chapters from "Goodman & Gilman's The Pharmacological Basis of Therapeutics" 11th ed by Brunton et al, and "Basic & Clinical Pharmacology" 11th ed. By Katzung et al.

I also perused Peck and Hill "Pharmacology for Anaesthesia and Intensive care" as well as the notoriously error-prone "Handbook of Pharmacology and Physiology in Anaesthetic Practice" by Stoelting and Hillier. Neither covered this subject in a depth I found satisfying.

Goodman and Gilman's remains a canonical text.