Inhibition of choline acetyltransferase by excess cysteine.

Abstract

THE first demonstrations of an enzyme that would synthesize acetylcholine (ACh)—originally designated choline acetylase but now called choline acetyltransferase (acetyl-CoA: choline-O-acetyltransferase, EC 2.3.1.6.)—depended on the presence in the tissues of other endogenous enzymes which would synthesize acetyl-CoA. Even when the substrate role of acetyl-CoA had been appreciated, however, it was found that in order to realize the maximal activity of the enzyme, provision had to be made to couple it with another enzyme system which would produce acetyl-CoA continuously from suitable precursors. Compared with the production from such coupled systems the amount of ACh produced from added synthetic acetyl-CoA was as little as 20 per cent in the experiments of Reisberg1 and about 50 per cent in those of Smallman2 and of Morris and Tucek3. However, McCaman and Hunt4 have obtained proportionately much higher yields of ACh in a buffer-substrate system containing synthetic acetyl-CoA, choline, eserine, magnesium sulphate, bovine plasma albumin and a high concentration of sodium chloride. Their incubations were conducted at pH 7.4. These authors considered that their higher yields of ACh depended on the replacement of potassium with a high concentration of sodium ions, but it appears that other factors may be more important.