ACETOACETATE METABOLISM IN AS-30D HEPATOMA-CELLS
ACETOACETATE METABOLISM IN AS-30D HEPATOMA-CELLS
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DOI：
10.1007/bf00926073
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发表时间：
1994-07-27
影响因子：
4.3
通讯作者：
KELLEHER, JK
中科院分区：
文献类型：
--
作者：
BRISCOE, DA;FISKUM, G;KELLEHER, JK
实验性肝癌细胞的代谢特征包括糖酵解和脂质合成的速率升高。然而，来自葡萄糖的丙酮酸不会被快速氧化，并且在As-39 D细胞中用于脂质合成的乙酰辅酶A的来源尚未被表征。本研究检测了AS-30 D肝癌细胞中酮体作为乙酰CoA的可能来源。主要发现有：1。AS-30 D细胞主要利用乙酰乙酸，[3-C-14]乙酰乙酸的主要产物为C-14-脂类和（CO2）-C-14.由乙酰乙酸酯合成脂质依赖于培养基中葡萄糖的存在.乙酰乙酸支持AS-30 D线粒体在0.1 mM苹果酸存在下的快速呼吸。AS-30 D线粒体中的琥珀酸CoA乙酰乙酰CoA转移酶活性比大鼠肝脏中发现的高约40倍。添加乙酰乙酸而不是β-羟基丁酸降低了[1-C-14]乙酸向（CO2）-C-14的转化，推测是通过稀释来自乙酸示踪剂的乙酰CoA的比放射性。在葡萄糖的存在下，约四分之一的乙酰乙酸被转化为脂质。这一结果与由截短的TCA循环假说所假设的脂肪生成升高一致。这些数据首次证明了乙酰乙酸碳在肝癌细胞中向脂质和CO2的通量，并表明乙酰乙酸周围浓度的增加，发生在空腹或恶性恶病质中，可能会增加含有3-含氧酸CoA转移酶活性的肝癌细胞对酮体的利用。
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. Acetoacetate was utilized by AS-30D cells, with C-14-lipid and (CO2)-C-14 as major products of [3-C-14] acetoacetate.2. Lipid synthesis from acetoacetate was dependent on the presence of glucose in the medium.3. Acetoacetate supported 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-hydroxybutyrate decreased conversion of [1-C-14] acetate to (CO2)-C-14, presumably by diluting the specific radioactivity of the acetyl CoA derived from the acetate tracer.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.