A RE-EVALUATION OF THE ROLE OF MITOCHONDRIAL PYRUVATE TRANSPORT IN THE HORMONAL-CONTROL OF RAT-LIVER MITOCHONDRIAL PYRUVATE METABOLISM
A RE-EVALUATION OF THE ROLE OF MITOCHONDRIAL PYRUVATE TRANSPORT IN THE HORMONAL-CONTROL OF RAT-LIVER MITOCHONDRIAL PYRUVATE METABOLISM
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DOI：
10.1042/bj2230677
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发表时间：
1984-01-01
影响因子：
4.1
通讯作者：
ARMSTON, AE
中科院分区：
文献类型：
--
作者：
HALESTRAP, AP;ARMSTON, AE
线粒体丙酮酸转运的抑制剂α-氰基-β-（1-苯基吲哚-3-基）丙烯酸酯用于抑制来自对照和胰高血糖素处理的大鼠的肝线粒体进行性丙酮酸羧化。与以前的结论相反，丙酮酸转运不能调节代谢在这些条件下。这一点通过测量线粒体内丙酮酸浓度得到证实，在对照线粒体中，线粒体内丙酮酸浓度几乎与线粒体外丙酮酸浓度平衡，但在胰高血糖素处理的大鼠线粒体中显著降低，其中丙酮酸代谢速率升高。计算机模拟研究解释了这如何与α-葡萄糖抑制丙酮酸代谢的线性狄克逊图相容。氰基-4-羟基肉桂酸酯。平行测量的线粒体膜电位通过使用[3 H]三苯基甲基磷离子表明，它升高了约3 mV的大鼠胰高血糖素和苯丙氨酸预处理后。跨膜pH梯度无显著变化。丙酮酸代谢的增加可以解释为呼吸链的刺激，产生质子动力的升高和线粒体内ATP/ADP比率的相应升高，这反过来又增加丙酮酸羧化酶活性。Amytal对呼吸链的轻度抑制逆转了激素处理对线粒体丙酮酸代谢和ATP浓度的影响，但对瓜氨酸合成无影响。这些观察结果的意义，从L-乳酸在体内的激素调节histogenesis进行了讨论。
The inhibitor of mitochondrial pyruvate transport .alpha.-cyano-.beta.-(1-phenylindol-3-yl)acrylate was used to inhibit progressively pyruvate carboxylation by liver mitochondria from control and glucagon-treated rats. Contrary to previous conclusions, pyruvate transport could not regulate metabolism under these conditions. This was confirmed by measuring the intramitochondrial pyruvate concentration, which almost equilibrated with the extramitochondrial pyruvate concentration in control mitochondria, but was significantly decreased in mitochondria from glucagon-treated rats, where rates of pyruvate metabolism were elevated. Computer-simulation studies explain how this is compatible with linear Dixon plots of the inhibition of pyruvate metabolism by .alpha.-cyano-4-hydroxycinnamate. Parallel measurements of the mitochondrial membrane potential by using [3H]triphenylmethylphosphonium ions showed that it was elevated by about 3 mV after pretreatment of rats with both glucagon and phenylephrine. There was no significant change in the transmembrane pH gradient. The increase in pyruvate metabolism can be explained by a stimulation of the respiratory chain, producing an elevation in the protonmotive force and a consequnt rise in the intramitochondrial ATP/ADP ratio, which in turn increases pyruvate carboxylase activity. Mild inhibition of the respiratory chain with Amytal reversed the effects of hormone treatment on mitochondrial pyruvate metabolism and ATP concentrations, but not on citrulline synthesis. The significance of these observations for the hormonal regulation of gluconeogenesis from L-lactate in vivo is discussed.