Enzyme inhibitors choline acetyltransferase

The reaction of choline with mitochondrial bound acetylcoenzyme A is catalysed by the cytoplasmic enzyme choline acetyltransferase (ChAT) (see Fig. 6.1). ChAT itelf is synthesised in the rough endoplasmic reticulum of the cell body and transported to the axon terminal. Although the precise location of the synthesis of ACh is uncertain most of that formed is stored in vesicles. It appears that while ChAT is not saturated with either acetyl-CoA or choline its synthesising activity is limited by the actual availability of choline, i.e. its uptake into the nerve terminal. No inhibitors of ChAT itself have been developed but the rate of synthesis of ACh can, however, be inhibited by drugs like hemicholinium or triethylcholine, which compete for choline uptake into the nerve. 

Other inhibitors depress the synthesis of acetylcholine in the motor nerve terminals, e.g. triethylcholine 7.43) (Bull and Hemsworth, 1965) and the more complex hemicholinium (Schueler, 1956). These agents interfere with choline transport and hence deprive acetyltransferase of its substrate also their action is reversed by choline (cf. Macintosh, Birks and Sastry, 1956). Glycollic acids bearing liposoluble substituents (e.g. p-phenylmande-lic acid) inhibit this enzyme in the brain (Holan, 1965). 

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