Abstract
Evidence has been provided for the assumption that the energy released by the breakdown of phosphocreatine is adequate to account for the electric energy released by the nerve action potential 1 Hence if the primary event responsible for the alterations of the nerve membrane during the passage of the impulse is the release of acetylcholine, as recently suggested, 3 , 4 energy rich phosphate bonds should be used for reversing the process and rebuilding the ester. In accordance with this hypothesis an enzyme, choline acetylase, has been extracted from brain which in presence of adenosine-triphosphate under strictly anaerobic conditions synthesizes acetylcholine in cell free solution. From 1 g fresh rat brain an enzyme solution may be prepared which forms 100-150 μg of acetylcholine (ACh) per hour. Presence of eserine and fluoride is necessary to inhibit the action of choline esterase and adenosinetriphosphatase. The enzyme contains active sulfhydryl groups which may be easily oxidized and are readily inactivated by monoiodoacetic acid or Cu in low concentrations. 5 On dialysis choline acetylase rapidly loses its activity. Addition of the natural l (+) glutamic acid reactivates it partly. 6 With potassium + glutamic acid 50-80% of the original activity may be restored; further addition of cyanide or replacement of glutamic acid by cysteine may reactivate the enzyme nearly completely. 7 , 8 The experiments suggest that the enzyme may require besides active -SH groups and potassium the presence of an amino acid group.
It has now been found that oxidized amino acids, i.e., α-keto acids, are strong inhibitors of choline acetylase. Pyruvic acid, a-keto-glutaric acid, phenyl- and oxyphenyl pyruvic acid have been tested so far. They inhibit choline acetylase in concentrations of 10-3 to 10-4 M. Table I gives a few significant data.
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