The Utilization of Choline and Acetyl Coenzyme A for the Synthesis of Acetylcholine

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Abstract
Acetylcholine synthesis in rat brain synaptosomes was investigated with regard to the intracellular sources of its 2 precursors, acetyl coA and choline. Investigations with .alpha.-cyano-4-hydroxycinnamate, an inhibitor of mitochondrial pyruvate transport, indicated that pyruvate must be utilized by pyruvate dehydrogenase located in the mitochondria, rather than in the cytoplasm. Evidence for a small, intracellular pool of choline available for acetylcholine synthesis was obtained under 3 experimental conditions. Bromopyruvate competitively inhibited high-affinity choline transport, perhaps because of accumulation of intracellular choline which was not acetylated when acetyl coA production was blocked. Choline accumulated under high-affinity transport conditions while acetyl coA production was resumed. Newly synthesized acetylcholine had a lower specific activity than that of choline in the medium. The acetyl coA that is used for the synthesis of acetylcholine may be derived from mitochondrial pyruvate dehydrogenase. A small pool of choline within cholinergic nerve endings may be available for acetylcholine synthesis, supporting the proposal that the high-affinity transport and acetylation of choline are kinetically coupled.