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Acetoacetate metabolism in AS-30D hepatoma cells

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Abstract

Metabolic characteristics of experimental hepatoma cells include elevated rates of glycolysis and lipid synthesis. However, pyruvate derived from glucose is not redily oxidized, and the source of acetly CoA for lipid synthesis in As-39D cells has not been characterized. In this study ketone bodies were examined as a possible source of acetyl CoA in AS-30D hepatoma cells.

The major findings were:

  1. 1.

    Acetoacetate was utilized by AS-30D cells, with14C-lipid and14CO2 as major products of [3-14C] acetoacetate.

  2. 2.

    Lipid synthesis from acetoacetate was dependent on the presence of glucose in the medium.

  3. 3.

    Acetoacetate supported rapid respiration by AS-30D mitochondria in the presence of 0.1 mM malate.

  4. 4.

    Succinly CoA acetoacetyl CoA transferase activity in AS-30D mitochondria was approximately 40 fold greater than that found in rat liver mitochondria.

  5. 5.

    Addition of acetoacetate, but not β-hydroxybutyrate decreased conversion of [1-14C] acetate to14CO2, presumably by diluting the specific radioactivity of the acetyl CoA derived from the acetate tracer.

  6. 6.

    In the presence of glucose, approximately one fourth of acetoacetate utilized was converted to lipid. This result is consistent with elevated lipogenesis postulated by the truncated TCA cycle hypothesis. These data demonstrate for the first time the flux of acetoacetate carbon to lipid and CO2 in hepatoma cells and suggest that increases in the ambient concentration of acetoacetate, occurring in fasting or malignant cachexia, could produce increases in the utilization of this ketone body by hepatoma cells containing 3-oxyacid CoA transferase activity.

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Briscoe, D.A., Fiskum, G., Holleran, A.L. et al. Acetoacetate metabolism in AS-30D hepatoma cells. Mol Cell Biochem 136, 131–137 (1994). https://doi.org/10.1007/BF00926073

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Key words

  • Hepatoma
  • acetoacetate
  • ketone bodies
  • 3-oxyacid CoA transferase
  • lipogenesis
  • tricarboxylic acid cycle