Effect of Cysteine on Acetylcholine Synthesis

Abstract

CHOLINE acetyltransferase (choline acetylase; acetyl-CoA: choline O-acetyltransferase, EC 2.3.1.6) (ChA) is a sulphydryl enzyme responsible for the synthesis of acetylcholine (ACh) in nervous and other tissues. Early attempts to purify ChA from rat brain and calf caudate nucleus showed that this enzyme is unstable and attempts were made to protect it by addition of cysteine to the medium. It was observed, however, that high concentrations of cysteine decreased the synthesis of ACh. Similar findings were recently reported by Morris, Hebb and Bull¹ in Torpedo Marmorata and rabbit brain extracts. They attributed the decreased synthesis of ACh to the inhibition of ChA by cysteine. Subsequently, Morris² studied the effect of a number of sulphydryl compounds on ChA activity. He demonstrated that their mode of action was not directly on ChA but that they acted by depletion of the acetyl-CoA in the system. We have been able to produce evidence to support Morris's suggestion that the reaction involved is a spontaneous transacetylation between acetyl-CoA and cysteine. This mechanism presumably applies to the other sulphydryl compounds which he studied.