title: 2-Oxoglutarate: oxidation and role as a potential precursor of cytosolic acetyl-CoA for the synthesis of acetylcholine in rat brain synaptosomes.
abstract: The possibility that 2-oxoglutarate may supply acetyl units for the cytosolic synthesis of acetylcholine in rat brain synaptosomes was investigated. The contribution of [14C]2-oxoglutarate to the synaptosomal synthesis of [14C]acetylcholine was found to be negligible despite evidence for its uptake and oxidation. The activity of the enzymes NADP-isocitrate dehydrogenase (EC 1.1.1.42), aconitate hydratase (EC 4.2.1.3), and ATP citrate-lyase (EC 4.1.3.8) were measured in the synaptosol. NADP-isocitrate dehydrogenase and aconitate hydratase are present at three- to 1.5-fold higher activities than ATP citrate-lyase. It seems likely that these enzymes contribute to the metabolism of citrate and prevent detectable formation of cytosolic acetyl-CoA from exogenously added 2-oxoglutarate (or citrate). The data further suggest that ATP citrate-lyase may in part be associated with the mitochondrial fraction.
authors.affiliation: Department of Biochemistry, St. Bartholomew's Hospital Medical College, University of London, England.
authors.forename: J
authors.initials: J
authors.lastname: Willoughby
authors.forename: F E
authors.initials: FE
authors.lastname: Craig
authors.forename: S A
authors.initials: SA
authors.lastname: Harvey
authors.forename: J B
authors.initials: JB
authors.lastname: Clark
mesh_terms: D001275:ATP Citrate (pro-S)-Lyase / Q000378:metabolism; D000105:Acetyl Coenzyme A / Q000378:metabolism*; D000109:Acetylcholine / Q000096:biosynthesis*; D000154:Aconitate Hydratase / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002245:Carbon Dioxide / Q000378:metabolism; D002250:Carbon Radioisotopes; D003600:Cytosol / Q000378:metabolism; D004072:Digitonin / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D007521:Isocitrate Dehydrogenase / Q000378:metabolism; D007656:Ketoglutaric Acids / Q000378:metabolism*; D008297:Male; D009997:Osmotic Pressure; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains; D013574:Synaptosomes / Q000378:metabolism*
chemical_list: D002250:Carbon Radioisotopes; D007656:Ketoglutaric Acids; D002245:Carbon Dioxide; D000105:Acetyl Coenzyme A; D007521:Isocitrate Dehydrogenase; C039355:isocitrate dehydrogenase (NADP+); D001275:ATP Citrate (pro-S)-Lyase; D000154:Aconitate Hydratase; D005947:Glucose; D004072:Digitonin; D000109:Acetylcholine