Acetylcholine - Metabolism
Biosynthesis
Acetylcholine is synthesized in two steps:
- Formation of acetyl coenzyme A, AcCoA, CoA S CO-CH3, from acetate and coenzyme A, CoA HS, (A for acetylation), according to the following reaction, catalyzed by AcCoA synthetase, limiting step of the synthesis.
AcCoA synthase
Acetate + CoenzymeA ¾¾¾® AcCoA
- Then formation of acetylcholine from choline and AcCoA, catalyzed by choline acetylase called also choline acetyltransferase.
Choline acetyltransferase
AcCoA + choline ¾¾¾¾® Acetylcholine
Choline present in tissues has two origins: exogenous, in food, and endogenous, by biosynthesis from glycine through many steps: serine, ethanolamine, phosphatidyl-ethanolamine, phosphatidyl-choline and choline. The trimethylation of phosphatidyl-ethanolamine needs the presence of vitamin B12, folic acid and methionine.
Distribution
Tissue distribution of acetylcholine is very broad. It is present:
- in the central nervous system: brain, spinal cord, nerve.
- in the vegetative nervous system: in sympathetic and parasympathetic ganglia and in parasympathetic terminations.
- In presynaptic terminations of neuromuscular junctions.
Release
In presynaptic terminations, acetylcholine is contained in vesicles. Nervous impulse, i.e. action potential, induces migration of vesicles towards the membrane and release of acetylcholine into the synaptic cleft.
The stimulation of presynaptic muscarinic receptors inhibits acetylcholine release and, conversely, their inhibition increases it.
Botulinum toxin is an inhibitor of the acetylcholine release.
Inactivation
Tissues which contain acetylcholine and enzymes involved in its synthesis, contain also cholinesterases which hydrolyze acetylcholine, which explains the fugacious activity of acetylcholine.
Two types of cholinesterases have been distinguished according to their affinities for different substrates, endogenous such as acetylcholine, and exogenous such as acetyl-ß-méthylcholine, butyrylcholine and benzoylcholine.
- Acetylcholinesterase, present in nervous tissue and erythrocytes, very quickly hydrolyzes acetylcholine and acetyl-ß-méthylcholine, but does not hydrolyze butyrylcholine. It is called true cholinesterase.
- Butyrylcholinesterase, present in tissues such as heart and plasma, hydrolyzes acetylcholine, benzoylcholine, butyrylcholine but not acetyl-ß-méthylcholine. It is called pseudo-cholinesterase.
Choline resulting from the hydrolysis of acetylcholine is reuptaken by the cholinergic terminations by an active mechanism, Na+ and Cl- dependant, inhibited by hemicholinium .
An enzymatic deficiency or an enzyme inhibition is detected by determination of activity of pseudo-cholinesterase in serum and of cholinesterase in red blood cells.
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