Interactions between pyruvate carboxylase and other mitochondrial enzymes.
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.
Fahien
L A
LA
Department of Pharmacology, University of Wisconsin Medical School, Madison 53706.
Davis
J W
JW
Laboy
J
J
D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D002417:Cattle; D002950:Citrate (si)-Synthase / Q000378:metabolism; D005969:Glutamate Dehydrogenase / Q000378:metabolism; D007655:Ketoglutarate Dehydrogenase Complex / Q000378:metabolism; D007700:Kinetics; D008291:Malate Dehydrogenase / Q000378:metabolism; D008928:Mitochondria / Q000201:enzymology*; D008929:Mitochondria, Heart / Q000201:enzymology; D008930:Mitochondria, Liver / Q000201:enzymology; D011766:Pyruvate Carboxylase / Q000378:metabolism*; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism; D013552:Swine
D011768:Pyruvate Dehydrogenase Complex; D008291:Malate Dehydrogenase; D007655:Ketoglutarate Dehydrogenase Complex; D005969:Glutamate Dehydrogenase; D002950:Citrate (si)-Synthase; D001219:Aspartate Aminotransferases; D011766:Pyruvate Carboxylase