Fahien L A, Davis J W, Laboy J
Department of Pharmacology, University of Wisconsin Medical School, Madison 53706.
J Biol Chem. 1993 Aug 25;268(24):17935-42.
Although pyruvate carboxylase associated with both mitochondrial aspartate aminotransferase and malate dehydrogenase, it had a higher affinity for the amino-transferase. Furthermore, the aminotransferase enhanced dissociation of malate dehydrogenase from pyruvate carboxylase. Glutamate dehydrogenase did not associate with pyruvate carboxylase alone, but it apparently associated with the pyruvate carboxylase-aminotransferase complex, and malate dehydrogenase associated with the resulting ternary complex. Citrate synthase and other proteins tested did not associate with pyruvate carboxylase. However, citrate synthase associated with the pyruvate carboxylase-malate dehydrogenase complex. Apparently as a consequence of these heteroenzyme interactions, the rate of the pyruvate carboxylase reaction was slightly greater when coupled with malate dehydrogenase or both malate dehydrogenase and citrate synthase than when coupled with citrate synthase alone. In addition, in the presence of both coupling enzymes, the rate of conversion of pyruvate to citrate was higher than predicted on the basis of the Michaelis-Menten relationship of the two coupling enzymes. Therefore, binding of malate dehydrogenase to pyruvate carboxylase enhances pyruvate carboxylase activity. Association of citrate synthase with the malate dehydrogenase-pyruvate carboxylase binary complex does not alter activation of pyruvate carboxylase but results in citrate synthase being more reactive than free citrate synthase with oxalacetate.
尽管丙酮酸羧化酶与线粒体天冬氨酸氨基转移酶和苹果酸脱氢酶均相关联，但它对氨基转移酶具有更高的亲和力。此外，氨基转移酶增强了苹果酸脱氢酶与丙酮酸羧化酶的解离。谷氨酸脱氢酶不会单独与丙酮酸羧化酶结合，但它显然会与丙酮酸羧化酶 - 氨基转移酶复合物结合，而苹果酸脱氢酶会与形成的三元复合物结合。柠檬酸合酶和其他测试的蛋白质不会与丙酮酸羧化酶结合。然而，柠檬酸合酶会与丙酮酸羧化酶 - 苹果酸脱氢酶复合物结合。显然，由于这些异源酶相互作用，与苹果酸脱氢酶或同时与苹果酸脱氢酶和柠檬酸合酶偶联时，丙酮酸羧化酶反应的速率比仅与柠檬酸合酶偶联时略高。此外，在两种偶联酶都存在的情况下，丙酮酸向柠檬酸的转化速率高于根据两种偶联酶的米氏关系所预测的速率。因此，苹果酸脱氢酶与丙酮酸羧化酶的结合增强了丙酮酸羧化酶的活性。柠檬酸合酶与苹果酸脱氢酶 - 丙酮酸羧化酶二元复合物的结合不会改变丙酮酸羧化酶的激活，但会导致柠檬酸合酶比游离柠檬酸合酶对草酰乙酸更具反应性。
