The utilization of choline and acetyl coenzyme A for the synthesis of acetylcholine.
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.
D000105:Acetyl Coenzyme A / Q000378:metabolism*; D000107:Acetylation; D000109:Acetylcholine / Q000096:biosynthesis*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001921:Brain / Q000378:metabolism*; D002794:Choline / Q000378:metabolism*; D003373:Coumaric Acids / Q000494:pharmacology; D008297:Male; D009570:Nitriles / Q000494:pharmacology; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism; D011773:Pyruvates / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D013574:Synaptosomes / Q000378:metabolism*
D003373:Coumaric Acids; D009570:Nitriles; D011768:Pyruvate Dehydrogenase Complex; D011773:Pyruvates; C007175:alpha-cyano-4-hydroxycinnamate; C017092:bromopyruvate; D000105:Acetyl Coenzyme A; D002794:Choline; D000109:Acetylcholine