Cocarboxylase and the Synthesis of Acetylcholine

Abstract

Biochemical studies of nerves under electrical stimulation or at rest have shown that acetylcholine, regarded for a long time only as a transmitter of nervous impulses at synaptic levels, is present in appreciable amounts in the nerve fiber itself. 1 We have proved that extracts from stimulated nerves produce a more intense action on the dorsal muscle of the leech than extracts from nerves at rest. This finding led us to consider the part played 1by acetylcholine in the phenomenon of nerve conduction. An analysis of the observed effects enabled us to reach the conclusion that excitation is followed not only by an increase in the amount of acetylcholine in nerves but also by the formation of an unknown substance appearing in the system and capable of sensitizing the reactive muscle. Further work has made clear analogies of action between this unknown substance and thiamin and has enabled us to prove that stimulated nerve liberates an amount of thiamin many times greater than that given off by the nerve at rest. 1 Since the amount of thiamin which sensitizes the muscle of the leech to acetylcholine is much smaller than that which would inactivate cholinesterase, we concluded that the vitamin plays a part in the synthesis of the chemical transmitter.

Thiamin is active in organisms in the form of thiamin pyrophosphate or cocarboxylase. Therefore, it seemed desirable to determine whether this coenzyme may play a part in the synthesis of acetylcholine from choline. A contracture of the dorsal muscle of the leech may be obtained with relatively high doses of choline. But contrary to the reaction produced by acetylcholine, this effect is not increased by eserine. 2 , 3 If cocarboxylase is capable of transforming choline into acetylcholine, the mixture of both should exert an action on the muscle which is increased by eserine.