Mechanisms of acetylcholine synthesis by rat brain choline acetyltransferase and its regulation by products and inhibitors
Choline acetyltransferase (EC 184.108.40.206, ChA) is the enzyme which catalyses the synthesis of acetylcholine (ACh) from acetylcoenzyme A and choline. According to available information, ChA may be bound to the outside membrane of the synaptic vesicle and so it is reasonable to assume that ACh is synthesised in the cytoplasm of the synaptosome and conveyed to the vesicle by an uptake mechanism. There is no convincing evidence, however, that there is an ACh-uptake system in the vesicular membrane (Whittaker, 1973). An alternate possibility is that the substrates choline and acetylcoenzyme A may bind to ChA from the outside surface of the vesicle, although the first product (ACh) is released towards the inside surface of the vesicle and the second product (coenzyme A) dissociates into the cytoplasm of the synaptosome. According to this alternative possibility, the presence of an ACh-uptake system is not necessary for accumulation of ACh into the vesicle. For the verification of such a possibility, we have investigated the kinetic mechanism for the synthesis of ACh by the rat brain ChA.
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