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

Richard S. Jope, Donald J. Jenden

Research output: Contribution to journalArticle

34 Scopus citations

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 (US)
Pages (from-to)318-325
Number of pages8
JournalJournal of neurochemistry
Volume35
Issue number2
DOIs
StatePublished - Aug 1980
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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