Synthesis of acetylcholine involves the reaction of acetyl-coenzyme A (acetyl-CoA) and choline, catalysed by the enzyme choline acetyltransferase. Acetyl-CoA is synthesized in the mitochondria of the axon terminals from pyruvate. About 50% of the choline is derived from the breakdown of Ach; the remaining is extracted from the extracellular fluid by a Na+ -dependent active transport process in the cell membrane which is the rate-limiting step in Ach synthesis. Choline acetyltransferase is originally synthesized on the ribosomes in the cell bodies of motor neurones and transported distally by axoplasmic flow to the nerve terminals, where high concentration can be detected. Enzyme activity is inhibited by acetylcholine but enhanced by nerve stimulation (Figure MP.16).
Figure MP.15 Acetylcholine receptor structure
Ach molecules are stored in the vesicles situated in the nerve endings. Each vesicle contains about 4000 molecules of Ach. There appears to be different stores of vesicles that differ in their availability for release, depending on the level of demand (nerve stimulation). Thus there are the readily releasable store (80%) and the stationary store (20%).
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