Abstract
In potassium-depolarized synaptosomes Ca2+ inhibited oxidation of pyruvate (30%) and decreased the level of acetyl-CoA in intrasynaptosomal mitochondria (32%). On the other hand, Ca2+ facilitated provision of acetyl-CoA to synaptoplasm, since under these condition no change of synaptoplasmic acetyl-CoA and twofold stimulation of acetylcholine synthesis were found. However, in Ca2+-activated synaptosomes both synaptoplasmic acetyl-CoA and acetylcholine synthesis were suppressed by 1 mM (−)hydroxycitrate by 27 and 29%, respectively. It was not the case in resting synaptosomes. Dichloroacetate (0.05 mM) partially reversed the inhibitory effect of Ca2+ on pyruvate metabolism in synaptosomes and whole brain mitochondria. In Ca2+-stimulated synaptosomes, the dichloroacetate overcame suppressive effects of (−)hydroxycitrate on the level of synaptoplasmic acetyl-CoA and acetylcholine synthesis, but not on citrate clevage. It is concluded that dichloroacetate may improve the metabolism of acetylcholine in activated cholinergic terminals by increasing the production of acetyl-CoA in mitochondria and increasing its provision through the mitochondrial membrane to synaptoplasm by the transport system, independent of the ATP-citrate lyase pathway.
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Szutowicz, A., Bielarczyk, H. & Skulimowska, H. Effect of dichloroacetate on acetyl-CoA content and acetylcholine synthesis in rat brain synaptosomes. Neurochem Res 19, 1107–1112 (1994). https://doi.org/10.1007/BF00965142
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DOI: https://doi.org/10.1007/BF00965142