丙酮酸浓度、二氯乙酸和α-氰基-4-羟基肉桂酸对分离的大鼠肝细胞糖异生、酮体生成及[3-羟基丁酸]/[3-氧代丁酸]比值的影响。
The effects of pyruvate concentration, dichloroacetate and alpha-cyano-4-hydroxycinnamate on gluconeogenesis, ketogenesis and [3-hydroxybutyrate]/[3-oxobutyrate] ratios in isolated rat hepatocytes.
作者信息
Demaugre F, Leroux J P, Cartier P
出版信息
Biochem J. 1978 Apr 15;172(1):91-6. doi: 10.1042/bj1720091.
Abstract
- In isolated rat hepatocytes incubated with pyruvate, ketogenesis increased with increasing pyruvate concentrations and decreased under the influence of 1 mM-alpha-cyano-4-hydroxycinnamate, a known inhibitor of pyruvate transport. Ketogenesis from pyruvate was higher by 30% in hepatocytes prepared from starved than from fed rats. 2. With pyruvate as substrate, 2 mM-dichloroacetate had no effect on ketogenesis of starved-rat hepatocytes, but increased ketogenesis of fed-rat hepatocytes to the 'starved' value. Gluconeogenesis from pyruvate, lactate and alanine, but not from glycerol, was inhibited by dichloroacetate. Both increased ketogenesis and decreased gluconeogenesis may result from an inhibition of pyruvate carboxylase by dichloroacetate. 3. Mitochondria were rapidly isolated from incubated hepatocytes, and [3-hydroxybutyrate]/[3-oxobutyrate] ratios were measured in the mitochondrial pellet ('mitochondrial' ratios) and in whole-cell suspensions ('total' ratios). Increasing pyruvate concentrations increased mitochondrial and decreased total ratios. In the presence of pyruvate (2 to 10 mM), dichloroacetate decreased mitochondrial and increased total ratios.
摘要
- 在与丙酮酸一起孵育的分离大鼠肝细胞中，酮体生成随着丙酮酸浓度的增加而增加，并在1 mM-α-氰基-4-羟基肉桂酸（一种已知的丙酮酸转运抑制剂）的影响下减少。饥饿大鼠制备的肝细胞中由丙酮酸生成酮体的量比喂食大鼠制备的肝细胞高30%。2. 以丙酮酸为底物时，2 mM二氯乙酸对饥饿大鼠肝细胞的酮体生成没有影响，但将喂食大鼠肝细胞的酮体生成增加到“饥饿”值。二氯乙酸抑制了由丙酮酸、乳酸和丙氨酸而非甘油进行的糖异生。酮体生成增加和糖异生减少都可能是由于二氯乙酸抑制了丙酮酸羧化酶。3. 从孵育的肝细胞中快速分离出线粒体，并测量线粒体沉淀中的[3-羟基丁酸酯]/[3-氧代丁酸酯]比值（“线粒体”比值）和全细胞悬浮液中的比值（“总”比值）。增加丙酮酸浓度会增加线粒体比值并降低总比值。在存在丙酮酸（2至10 mM）的情况下，二氯乙酸会降低线粒体比值并增加总比值。
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