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Choline Acetyltransferase and the Synthesis of Acetylcholine

  • Chapter
The Cholinergic Synapse

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 86))

Abstract

Soon after the discovery that acetylcholine (ACh) mediates synaptic transmission in sympathetic ganglia, Brown and Feldberg (1936) noted that the amount of ACh released from perfused stimulated ganglia during their experiments was several-fold higher than the amount of ACh that had been present in the ganglia at the start of the experiments. It became apparent from this and other observations that ACh is synthesized in the nerve terminals which use it as their transmitter and that the rate of its synthesis varies so as to keep the stores of ACh in the nerve terminals at a constant level under most physiological conditions. Systematic studies of the process of ACh synthesis were started by Quastel and Mann (Quastel et al. 1936, Mann et al. 1938, 1939) and by Stedman and Stedman (1937). In a few years, Nachmansohn and Machado (1943) proved able to demonstrate the synthesis of ACh in cell-free tissue extracts with added ATP, acetate and choline; they ascribed the synthesis to the activity of a new enzyme which they called ‘choline acetylase’. It has been clarified in the following work that at least two enzymes must have been active in the system used by Nachmansohn and Machado (1943), one enzyme producing acetylcoenzyme A (AcCoA) from acetate, coenzyme A (CoA) and ATP (AcCoA synthetase by the present nomenclature), and another enzyme producing ACh from AcCoA and choline. The name of choline acetylase was preserved for the latter enzyme and was modified to choline acetyltransferase (acetyl-CoA: choline-O-acetyltransferase, EC 2.3.1.6) (ChAT) in the EC-IUB enzyme nomenclature.

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Tuček, S. (1988). Choline Acetyltransferase and the Synthesis of Acetylcholine. In: Whittaker, V.P. (eds) The Cholinergic Synapse. Handbook of Experimental Pharmacology, vol 86. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-73220-1_7

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