Topic
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.
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TL;DR: The findings provide the basis for the therapeutic implication of hordenine and its derivatives in lung cancer and PDK3-related diseases after required in vivo validation.
Abstract: Design and development of potential pyruvate dehydrogenase kinase 3 (PDK3) inhibitors have gained attention because of their possible therapeutic uses in lung cancer therapy. In the present study, the binding affinity of naturally occurring alkaloids, hordenine, vincamine, tryptamine, cinchonine, and colcemid was measured with PDK3. The molecular docking and fluorescence binding studies suggested that all these compounds show a considerable binding affinity for PDK3. Among them, the affinity of hordenine to the PDK3 was excellent (K = 106 M−1) which was further complemented by isothermal titration calorimetric measurements. Hordenine binds in the active site pocket of PDK3 and forms a significant number of non-covalent interactions with functionally important residues. All-atom molecular dynamics (MD) simulation study suggested that the PDK3-hordenine complex is stabilized throughout the trajectory of 100ns and leads to fewer conformational changes. The enzyme inhibition studies showed that hordenine inhibits the activity of PDK3 with an IC50 value of 5.4 µM. Furthermore, hordenine showed a cytotoxic effect on human lung cancer cells (A549 and H1299) with an admirable IC50 value. However, it did not inhibit the growth of HEK293 cells up to 200 µM, indicating its non-toxicity to non-cancerous cell lines. In summary, our findings provide the basis for the therapeutic implication of hordenine and its derivatives in lung cancer and PDK3-related diseases after required in vivo validation.
65 citations
TL;DR: Pyruvate (2 to 60 mM), acting alone and in conjunction with insulin and epidermal growth factor (EGF), enhances DNA synthesis in primary monolayer cultures of adult rat liver parenchymal cells.
Abstract: Pyruvate (2 to 60 mM), acting alone and in conjunction with insulin and epidermal growth factor (EGF), enhances DNA synthesis in primary monolayer cultures of adult rat liver parenchymal cells. Lactate can replace pyruvate in stimulating DNA synthesis. Several other intermediary metabolites (oxaloacetate, α-ketoglutarate, α-ketobutyrate, succinate, fumarate, and malate), though less potent than pyruvate and lactate, also elevate DNA synthesis, whereas alanine at similar concentrations is inhibitory.
65 citations
TL;DR: The respiration of Pichia stipitis was not repressed by either high concentrations of fermentable sugars or oxygen limitation, and pyruvate decarboxylase was not inhibited by phosphate.
Abstract: The respiration of Pichia stipitis was not repressed by either high concentrations of fermentable sugars or oxygen limitation Fermentation was not induced by high sugar concentrations, but was inactivated by aerobic conditions The activity of pyruvate dehydrogenase was constitutive In contrast, pyruvate decarboxylase, alcohol dehydrogenase, and aldehyde dehydrogenase were induced by a reduction in the oxygen tension It was demonstrated that in P stipitis, the pyruvate decarboxylase is not induced by a signal from glycolysis Contrary to Saccharomyces cerevisiae, the pyruvate decarboxylase was not inhibited by phosphate
65 citations
01 Jan 1968
65 citations
TL;DR: This study examines recombinant protein production in Escherichia coli containing activity in an additional anaplerotic enzyme, pyruvate carboxylase, and indicates that acetate concentration does not limit cell growth and protein synthesis, and suggests instead that the rate of acetate formation represents an inefficient consumption of glucose carbon, which is reduced by the presence of pyruVate car boxylase.
Abstract: Anaplerotic enzyme reactions are those which replenish tricarboxylic acid intermediates that are withdrawn for the synthesis of biomass. In this study, we examined recombinant protein production in Escherichia coli containing activity in an additional anaplerotic enzyme, pyruvate carboxylase. In batch fermentations, the presence of pyruvate carboxylase resulted in 68% greater production of the model protein, β-galactosidase, 41% greater cell yield, and 57% lower acetate concentration. We discuss why these results indicate that acetate concentration does not limit cell growth and protein synthesis, as predicted by other researchers, and suggest instead that the rate of acetate formation represents an inefficient consumption of glucose carbon, which is reduced by the presence of pyruvate carboxylase.
65 citations