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Contributions of Cytosolic and Mitochondrial Acetyl-CoA Syntheses to the Activation of Lipogenic Acetate in Rat Liver

  • Robert P. Goldberg
  • Henri Brunengraber

Summary

Acetate derived from ethanol oxidation is activated by cytosolic and mitochondrial acetyl-CoA synthetases before contributing to the extra-mitochondrial processes of fatty acid and 3-β-hydroxysterol synthesis. Mitochondrially-generated acetyl-CoA is transferred to the cytosol via citrate and ATP-citrate lyase; this transfer is blocked by (-)-hydroxycitrate. Rats were injected IV with 3.3 mmol/kg of [2-3H,2-14C] acetate and IP with either 0.5 mmol/kg hydroxycitrate or saline. After one hour, the rats were killed and the incorporation of label was measured in liver fatty acids and 3-β-hydroxysterols. The 3H/14C ratio was increased by 12 and 13% in the fatty acids and 3-β-hydroxysterols of the hydroxycitrate-treated group. The lower ratio in the fatty acids and 3-β-hydroxysterols derived from mitochondrially-generated acetylCoA is ascribed to a loss of 3H in the citrate synthase reaction. The data showed that (1) fatty acids and 3-β-hydroxysterols syntheses use the same pool of cytosolic acetyl-CoA; and (2) in the absence of an isotope effect in the citrate synthase reaction, mitochondrially-generated acetyl-CoA contributes about 36% to lipogenesis from acetate.

Keywords

Isotope Effect Mitochondrial Pathway Ethanol Oxidation Liver Fatty Acid Acid Sterol 
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References

  1. Brunengraber, H., M. Boutry, and J.M. Lowenstein, 1973, Fatty acid and 3-ß-hydroxysterol synthesis in the perfused rat liver, J. Biol. Chem., 248: 2656.PubMedGoogle Scholar
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Copyright information

© Springer Science+Business Media New York 1980

Authors and Affiliations

  • Robert P. Goldberg
    • 1
  • Henri Brunengraber
    • 1
  1. 1.Department of Nutrition and Food ScienceMassachusetts Institute of TechnologyCambridgeUSA

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