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Synthesis and metabolism of acetylcholine

Choline
Choline CH3 This crucifix-shaped molecule is choline, a
quaternary saturated amine, which is an
essential water-soluble nutrient usually
CH3 N CH2 CH2 OH found complexed with B-vitamins.
Acetate anion Delicious natural sources are whole eggs
CH3 and the fatty animal meat.
O
In certain neurons, choline is metabolised
O- into acetylcholine; the extra acetyl group is
C CH3
donated by acetyl-CoA (which draws on
the inexhaustible supply of acetate anions
which are constantly burned in the citric
acid cycle).
Acetyl-CoA
Pyruvate Choline acetyltransferase The choline acyltransferase enzyme is
decarboxylation responsible for catalyzing this process.
It happens in the body of the neuron,
Coenzyme A
and the finished acetylcholine is
transported in vesicles via axoplasmic flow.
Acetylcholine
This is an ester of acetic acid
and choline. CH3 O

CH3 N CH2 CH2 O C CH3

CH3 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.
Acetylcholine esterase The acetate goes god knows where
(presumably back into Krebs cycle) and the
choline is dutifully reabsorbed by its uptake
O transporters ( of which there are two, one Na+
/Cl- dependent high affinity transporter and
O- C CH3 another independent transporter of lower
affinity).
CH3 This reuptake is the rate-limiting step in
acetylcholine synthesis.

CH3 N CH2 CH2 OH

CH3
Reuptake into the terminal

From Peck and Hill “Pharmacology for Anaesthesia and Intensive care” as well as the mighty “Handbook of Pharmacology and Physiology in Anaesthetic Practice” by Stoelting and Hillier. A