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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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Journal ArticleDOI
TL;DR: Findings help explain the unique effects of Leu compared with Val and Ile on branched-chain amino acid metabolism and the differences between control of the kinases associated with pyruvate dehydrogenase and brancher-chain α-ketoacid dehydrogenases.

155 citations

Journal ArticleDOI
TL;DR: Observations indicate that interactions of cytosolic proteins, such as the glycolytic enzymes, with cytoskeletal components,such as microtubules, may play a structural role in the formation of the microtrabecular lattice.

155 citations

Journal ArticleDOI
TL;DR: There is enough inner membrane present in the mitochondria to bind the dehydrogenases in the matrix space according to the amount of binding observed in these in vitro studies, and the possible metabolic significance of these interactions is discussed.

155 citations

Journal ArticleDOI
TL;DR: A differential gene expression screen is used to identify genes that are responsible for the physiological characteristics of hibernation in the heart of the thirteen-lined ground squirrel and reports that genes for pancreatic lipase and pyruvate dehydrogenase kinase isozyme 4 are up-regulated in theheart during hibernation.
Abstract: Hibernation is a physiological adaptation characterized by dramatic decreases in heart rate, body temperature, and metabolism, resulting in long-term dormancy. Hibernating mammals survive for periods up to 6 mo in the absence of food by minimizing carbohydrate catabolism and using triglyceride stores as their primary source of fuel. The cellular and molecular mechanisms underlying the changes from a state of activity to the hibernating state are poorly understood; however, the selective expression of genes offers one level of control. To address this problem, we used a differential gene expression screen to identify genes that are responsible for the physiological characteristics of hibernation in the heart of the thirteen-lined ground squirrel (Spermophilus tridecemlineatus). Here, we report that genes for pancreatic lipase and pyruvate dehydrogenase kinase isozyme 4 are up-regulated in the heart during hibernation. Pancreatic lipase is normally expressed exclusively in the pancreas, but when expressed in the hibernating heart it liberates fatty acids from triglycerides at temperatures as low as 0°C. Pyruvate dehydrogenase kinase isozyme 4 inhibits carbohydrate oxidation and depresses metabolism by preventing the conversion of pyruvate to Ac-CoA. The resulting anaerobic glycolysis and low-temperature lipid catabolism provide evidence that adaptive changes in cardiac physiology are controlled by the differential expression of genes during hibernation.

154 citations

Journal ArticleDOI
TL;DR: Although pyruvate kinase knockdown results in modest impairment of proliferation in vitro, in vivo growth of established xenograft tumors is unaffected by PKM2 absence, suggesting that other metabolic pathways bypass its function.
Abstract: Many cancer cells have increased rates of aerobic glycolysis, a phenomenon termed the Warburg effect. In addition, in tumors there is a predominance of expression of the M2 isoform of pyruvate kinase (PKM2). M2 expression was previously shown to be necessary for aerobic glycolysis and to provide a growth advantage to tumors. We report that knockdown of pyruvate kinase in tumor cells leads to a decrease in the levels of pyruvate kinase activity and an increase in the pyruvate kinase substrate phosphoenolpyruvate. However, lactate production from glucose, although reduced, was not fully inhibited. Furthermore, we are unique in reporting increased serine and glycine biosynthesis from both glucose and glutamine following pyruvate kinase knockdown. Although pyruvate kinase knockdown results in modest impairment of proliferation in vitro, in vivo growth of established xenograft tumors is unaffected by PKM2 absence. Our findings indicate that PKM2 is dispensable for tumor maintenance and growth in vivo, suggesting that other metabolic pathways bypass its function.

152 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
202329
202234
202161
202063
201959
201851