Pyruvate Utilization, Choline Uptake and Acetylcholine Synthesis

Abstract

This presentation will review the lines of evidence that indicate ACh synthesis can be sensitive to reduced carbohydrate utilization, and describe some recent experiments in which the effects of impaired carbohydrate utilization have been used to investigate the functional relationship between the high affinity transport of choline (Ch) and the synthesis of ACh. A glucose requirement for ACh synthesis was established in 1936 by Quastel et al. (29) in brain slices, and in 1939 by Karlson and MacIntosh (20) in sympathetic ganglia. Since that time both in vivo (35, 36) and in vitro (3, 6, 22, 34) investigations have shown that glucose and pyruvate are the primary sources of acetyl groups for ACh synthesis in brain tissue. Glucose is converted to pyruvate by glycolysis and pyruvate is converted to acetyl coenzyme A (Ac CoA) by CO₂ in the mitochondria by pyruvate dehydrogenase. Pyruvate dehydrogenase in the brain is regulated by phosphorylation (inactive form) and dephosphorylation (active form) which can be altered in vitro (17) and in vivo (18) by various treatments. The route of transfer of acetyl units out of the mitochondria to the site of ACh synthesis in the cytoplasm has not been clearly defined, though transport of citrate followed by the synthesis of AcCoA catalyzed by citrate lyase has received some support (4, 6, 33).