M. Lipton, E. Barron
Nov 1, 1946
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Influential Citations
22
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Journal
The Journal of biological chemistry
Abstract
A recent review by Feldberg (1) summarizes the results of other workers dealing with the synthesis of acetylcholine in vitro. It is known that acetylcholine can be synthesized by respiring brain tissue in oxygen in the presence of glucose, lactate, or pyruvate (24) or by homogenized brain. or brain extracts anaerobically in the presence of added adenosine triphosphate (ATP) (5, 6). The synthesis is accelerated by K+ and inhibited by Cafe (7). The enzyme system appears to require active sulfhydryl groups because air, iodoacetate, iodine, cystine, and Cu++ inhibit, while cysteine (7) augments the activity of preparations which have been partially inactivated by dialysis. ATP is specific for the synthesis, since neither adenosine diphosphate nor inosine triphosphate could be substituted for ATP (6). The need for a coenzyme in the reaction has also been suggested recently (8, 9). The requirement for. choline in the synthesis of acetylcholine is well established (3, 5). The source of the acetyl group is as yet unknown. Acetic acid has no effect on the synthesis of acetylcholine either aerobically or anaerobically (1, 2, 5, 6). Pyruvate was suggested as an aerobic source by Qua&l and his associates (2, 3) and by Baer (10) who synthesized acetylcholine non-enzymatically. Acetoacetate was suggested as an anaerobic source by Stedman and Stedman (11, 12). Citrate, glutamate, and cysteine have been shown by Nachmansohn and John to activate the synthesis of acetylcholine (7), while a-keto acids inhibit it, but the mechanisms of the activation and inhibition have not been described. In this paper data are presented to show that a completely soluble enzyme system which synthesizes acetylcholine can be extracted from mammalian brain preparations. With this enzyme system, the following components are required for the synthesis of acetylcholine: choline, ATP, a substance able to provide active acetate which may be either citrate, cia-aconitate, or acetoacetate, and a thermostable coenzyme of as yet unknown composition present in boiled yeast or animal tissue extracts.