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

J Neurochem. 1980 Aug;35(2):318-25. doi: 10.1111/j.1471-4159.1980.tb06267.x.


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 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, 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetyl Coenzyme A / metabolism*
  • Acetylation
  • Acetylcholine / biosynthesis*
  • Animals
  • Biological Transport / drug effects
  • Brain / metabolism*
  • Choline / metabolism*
  • Coumaric Acids / pharmacology
  • Male
  • Nitriles / pharmacology
  • Pyruvate Dehydrogenase Complex / metabolism
  • Pyruvates / metabolism
  • Pyruvates / pharmacology
  • Rats
  • Synaptosomes / metabolism*


  • Coumaric Acids
  • Nitriles
  • Pyruvate Dehydrogenase Complex
  • Pyruvates
  • alpha-cyano-4-hydroxycinnamate
  • bromopyruvate
  • Acetyl Coenzyme A
  • Choline
  • Acetylcholine