Compartmentation of acetyl CoA studied by analysis of tricarboxylic acid cycle acids and 3-hydroxybutyrate in bile of rats given [2,2,2-2H3]ethanol.
Acetate, 3-hydroxybutyrate, pyruvate, lactate, citrate, 2-oxoglutarate, succinate, fumarate and malate were analysed in rat bile by gas chromatography and gas chromatography/mass spectrometry of their O-melthyloxime-t-butyldimethylsilyl derivatives. The concentration of acetate increased to about 1.8 mmol/l after administration of [2,2,2-2H3]ethanol. Acetate was formed from ethanol to an extent of about 82% and retained all of the 2H at C-2, whereas 15% of the 2H had been lost in the tricarboxylic acid cycle intermediates and 24% in 3-hydroxybutyrate. Thus the exchange of 2H for 1H takes place after formation of acetyl CoA. For citrate and 3-hydroxybutyrate, 41% and 11% respectively was formed from [2,2,2-2H3]ethanol. These results indicate that different pools of acetyl CoA are used for the synthesis of ketone bodies and citrate, with the latter being derived from ethanol to a much larger extent. Smaller fractions of 2-oxoglutarate (16%) and succinate (5%) were derived from [2,2,2--2H3]ethanol, indicating significant contributions from amino acids.
Norsten
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Department of Physiological Chemistry, Karolinska Institute, Stockholm, Sweden.
Cronholm
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D020155:3-Hydroxybutyric Acid; D000085:Acetates / Q000378:metabolism; D000105:Acetyl Coenzyme A / Q000378:metabolism*; D000818:Animals; D001646:Bile / Q000378:metabolism*; D002250:Carbon Radioisotopes; D002264:Carboxylic Acids / Q000378:metabolism; D002951:Citrates / Q000378:metabolism; D019343:Citric Acid; D002952:Citric Acid Cycle; D003903:Deuterium; D000431:Ethanol / Q000378:metabolism*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006885:Hydroxybutyrates / Q000378:metabolism*; D007700:Kinetics; D011865:Radioisotope Dilution Technique; D051381:Rats; D011919:Rats, Inbred Strains
D000085:Acetates; D002250:Carbon Radioisotopes; D002264:Carboxylic Acids; D002951:Citrates; D006885:Hydroxybutyrates; D019343:Citric Acid; D000431:Ethanol; D000105:Acetyl Coenzyme A; D003903:Deuterium; D020155:3-Hydroxybutyric Acid