ACETOACETATE METABOLISM IN AS-30D HEPATOMA-CELLS

Metabolic characteristics of experimental hepatoma cells include eleva ted 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 s tudy ketone bodies were examined as a possible source of acetyl CoA in AS-30D hepatoma cells. The major findings were: 1. Acetoacetate was u tilized by AS-30D cells, with C-14-lipid and (CO2)-C-14 as major produ cts of [3-C-14] acetoacetate. 2. Lipid synthesis from acetoacetate was dependent on the presence of glucose in the medium. 3. Acetoacetate s upported rapid respiration by AS-30D mitochondria in the presence of 0 .1 mM malate. 4. Succinly CoA acetoacetyl CoA transferase activity in AS-30D mitochondria was approximately 40 fold greater than that found in rat liver mitochondria. 5. Addition of acetoacetate, but not beta-h ydroxybutyrate decreased conversion of [1-C-14] acetate to (CO2)-C-14, presumably by diluting the specific radioactivity of the acetyl CoA d erived from the acetate tracer. 6. In the presence of glucose, approxi mately one fourth of acetoacetate utilized was converted to lipid. Thi s result is consistent with elevated lipogenesis postulated by the tru ncated TCA cycle hypothesis. These data demonstrate for the first time the flux of acetoacetate carbon to lipid and CO2 in hepatoma cells an d suggest that increases in the ambient concentration of acetoacetate, occurring in fasting or malignant cachexia, could produce increases i n the utilization of this ketone body by hepatoma cells containing 3-o xyacid CoA transferase activity.