INHIBITION OF BACTERIAL AND MAMMALIAN CHOLINE ACETYLTRANSFERASES BY STYRYLPYRIDINE ANALOGUES

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Abstract
—Choline acetyltransferase was extracted from Lactobacillus plantarum by relatively gentle procedures involving penicillin treatment, osmotic shock and passage through a French pressure cell. After partial purification, the extract was compared with choline acetyltransferase of calf caudate nucleus for kinetic properties and response to a class of inhibitors which consists of analogues of styrylpyridine. Both enzymes obeyed a sequential mechanism with Michaelis constants for the bacterial enzyme, Km= 8 μm vs. acetyl‐CoA and 0·44 mm vs. choline; and for the caudate nucleus enzyme, Km= 15 μm vs. acetyl‐CoA and 0·8 mm vs. choline. Both were stabilized by dithiothreitol and EDTA.The extracts differed in that the bacterial enzyme was more labile and apparently was susceptible to conformational changes, which modified its response to the styrylpyridinetype inhibitors. The use of intact cells of Lactobacillus plantarum as an in vivo system for studying the inhibition of choline acetyltransferase by styrylpyridines was possible only for non‐quaternary analogues, which exist as an equilibrium mixture of charged and uncharged species.