The utilization of choline and acetyl coenzyme A for the synthesis of acetylcholine

Richard S Jope, D. J. Jenden

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Acetylcholine synthesis in rat brain synaptosomes was investigated with regard to the intracellular sources of its two precursors, acetyl coenzyme A and choline. Investigations with α-cyano-4-hydroxycinnamate, an inhibitor of mitochondrial pyruvate transport, indicated that pyruvate must be utilized by pyrvate dehydrogenase located in the mitochondria, rather than in the cytoplasm, as recently proposed. Evidence for a small, intracellular pool of choline available for acetylcholine synthesis was obtained under three experimental conditions. (1) Bromopyruvate competitively inhibited high-affinity choline transport, perhaps because of accumulation of intracellular choline which was not acetylated when acetyl coenzyme A production was blocked. (2) Choline that was accumulated under high-affinity transport conditions while acetyl coenzyme A production was impaired was subsequently acetylated when acetyl coenzyme A production was resumed. (3) Newly synthesized acetylcholine had a lower specific activity than that of choline in the medium. These results indicate that the acetyl coenzyme A that is used for the synthesis of acetylcholine is derived from mitochondrial pyruvate dehydrogenase and that there is a small pool of choline within cholinergic nerve endings available for acetylcholine synthesis, supporting the proposal that the high-affinity transport and acetylation of choline are kinetically coupled.

Original languageEnglish
Pages (from-to)318-325
Number of pages8
JournalJournal of Neurochemistry
Volume35
Issue number2
StatePublished - Jan 1 1980
Externally publishedYes

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Acetyl Coenzyme A
Choline
Acetylcholine
Pyruvic Acid
Oxidoreductases
Acetylation
Mitochondria
Nerve Endings
Synaptosomes
Cholinergic Agents
Rats
Brain
Cytoplasm

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

The utilization of choline and acetyl coenzyme A for the synthesis of acetylcholine. / Jope, Richard S; Jenden, D. J.

In: Journal of Neurochemistry, Vol. 35, No. 2, 01.01.1980, p. 318-325.

Research output: Contribution to journalArticle

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