Pyruvate dehydrogenase kinase

About: Pyruvate dehydrogenase kinase is a research topic. Over the lifetime, 4224 publications have been published within this topic receiving 161052 citations. The topic is also known as: [pyruvate dehydrogenase (lipoamide)] kinase & pyruvate dehydrogenase (lipoamide) kinase.

The relative significance of CO2-fixing enzymes in the metabolism of rat brain.

Abstract: To evaluate the relative significance of CO2-fixing enzymes in the metabolism of rat brain, the subcellular distribution of pyruvate carboxylase, phosphoenolpyruvate carboxykinase, NADP-isocitrate dehydrogenase and NADP-malate dehydrogenase, as well as the fixation of H14CO3− by the cytosol and the mitochondria was investigated. Pyruvate carboxylase and phosphoenol-pyruvate carboxykinase are mainly localized in the mitochondria whereas NADP-isocitrate dehydrogenase and NADP-malate dehydrogenase are present in both the cytosol and the mitochondria. In the presence of pyruvate rat brain mitochondria fixed H14CO3− at a rate of about 170 nmol/g of tissue/min whereas these organelles fixed negligible amounts of H14CO3− in the presence of α-ketoglutarate or phosphoenolpyruvate. Rat brain cortex slices fixed H14CO3− at a rate of about 7 nmol/g of tissue/min and it was increased by two-fold when pyruvate was added to the incubation medium. The carboxylation of α-ketoglutarate and pyruvate by the reversal of the cytosolic NADP-isocitrate dehydrogenase and NADP-malate dehydrogenase respectively was very low as compared to that by pyruvate carboxylase. The rate of carboxylation reaction of both NADP-isocitrate dehydrogenase and NADP-malate dehydrogenase was only about 1/10th of that of decarboxylation reaction of the same enzyme. It is suggested that under physiological conditions these two enzymes do not play a significant role in CO2-fixation in the brain. In rat brain cytosol, citrate is largely metabolized to α-ketoglutarate by a sequential action of aconitate hydratase and NADP-isocitrate dehydrogenase. The operation of the citrate-cleavage pathway in rat brain cytosol is demonstrated. The data show that among four CO2-fixing enzymes, pyruvate carboxylase, an anaplerotic enzyme, plays the major role in CO2-fixation in the brain.

Lin28/let-7 axis regulates aerobic glycolysis and cancer progression via PDK1

Abstract: The RNA-binding proteins Lin28A and Lin28B are known to have key roles in a variety of pathological states including cancer, obesity and diabetes. Here the authors show that Lin28A and -B alter cancer metabolism through let-7-mediated upregulation of pyruvate dehydrogenase kinase 1.