Hutson N J, Kerbey A L, Randle P J, Sugden P H
Prog Clin Biol Res. 1979;31:707-19.
In animal tissues the pyruvate dehydrogenase complex is regulated by product inhibition and by a phosphorylation-dephosphorylation cycle catalysed by a kinase and a phosphatase. Physiologic and molecular aspects of this regulation are reviewed, and the results of recent studies are described. Insulin deficiency in the rat (diabetes or starvation) is shown to inhibit the conversion of inactive (phospho-) complex into active (dephospho-) complex by the phosphatase by an effect on the substrate for the phosphatase (phosphorylated complex). This change is stable and persists during isolation, incubation, and extraction of mitochondria or purification of phosphorylated complex. The subunit ratios in the purified pig heart pyruvate dehydrogenase complex and the stoichiometry of phosphorylations have been determined by radioamidination and incorporation of 32P. The ratios of decarboxylase tetramer (alpha 2, beta 2) : dihydrolipoyl acetyltransferase monomer : dihydrolipoly dehydrogenase monomer were 1:1:0.5. Inactivation of the complex was accomplished by incorporation of a single phosphate into one alpha subunit of the decarboxylase tetramer. Two further phosphates are then incorporated and these additional phosphorylations inhibit reactivation of the complex by the phosphate. It is suggested that multisite phosphorylations may inhibit reactivation of the complex by the phosphatase in diabetes and in starvation.
在动物组织中，丙酮酸脱氢酶复合体受产物抑制以及由一种激酶和一种磷酸酶催化的磷酸化 - 去磷酸化循环的调节。本文综述了这种调节的生理学和分子学方面，并描述了近期研究的结果。大鼠胰岛素缺乏（糖尿病或饥饿）通过对磷酸酶底物（磷酸化复合体）的作用，抑制磷酸酶将无活性（磷酸化）复合体转化为有活性（去磷酸化）复合体。这种变化是稳定的，并且在分离、孵育、线粒体提取或磷酸化复合体纯化过程中持续存在。通过放射性酰胺化和32P掺入，已确定纯化的猪心丙酮酸脱氢酶复合体中的亚基比例以及磷酸化的化学计量。脱羧酶四聚体（α2，β2）：二氢硫辛酰胺乙酰转移酶单体：二氢硫辛酰胺脱氢酶单体的比例为1:1:0.5。复合体的失活是通过在脱羧酶四聚体的一个α亚基中掺入一个磷酸来实现的。然后再掺入另外两个磷酸，这些额外的磷酸化抑制磷酸酶对复合体的再激活。有人提出，多位点磷酸化可能在糖尿病和饥饿状态下抑制磷酸酶对复合体的再激活。
