scispace - formally typeset
Search or ask a question
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.


Papers
More filters
Journal ArticleDOI
07 Oct 2013-PLOS ONE
TL;DR: Diet-induced inhibition of pyruvate dehydrogenase may be an initiating event in decreased oxidation of glucose and increased reliance of the heart on fatty acids for energy production.
Abstract: Cardiac function depends on the ability to switch between fatty acid and glucose oxidation for energy production in response to changes in substrate availability and energetic stress. In obese and diabetic individuals, increased reliance on fatty acids and reduced metabolic flexibility are thought to contribute to the development of cardiovascular disease. Mechanisms by which cardiac mitochondria contribute to diet-induced metabolic inflexibility were investigated. Mice were fed a high fat or low fat diet for 1 d, 1 wk, and 20 wk. Cardiac mitochondria isolated from mice fed a high fat diet displayed a diminished ability to utilize the glycolytically derived substrate pyruvate. This response was rapid, occurring within the first day on the diet, and persisted for up to 20 wk. A selective increase in the expression of pyruvate dehydrogenase kinase 4 and inhibition of pyruvate dehydrogenase are responsible for the rapid suppression of pyruvate utilization. An important consequence is that pyruvate dehydrogenase is sensitized to inhibition when mitochondria respire in the presence of fatty acids. Additionally, increased expression of pyruvate dehydrogenase kinase 4 preceded any observed diet-induced reductions in the levels of glucose transporter type 4 and glycolytic enzymes and, as judged by Akt phosphorylation, insulin signaling. Importantly, diminished insulin signaling evident at 1 wk on the high fat diet did not occur in pyruvate dehydrogenase kinase 4 knockout mice. Dietary intervention leads to a rapid decline in pyruvate dehydrogenase kinase 4 levels and recovery of pyruvate dehydrogenase activity indicating an additional form of regulation. Finally, an overnight fast elicits a metabolic response similar to that induced by high dietary fat obscuring diet-induced metabolic changes. Thus, our data indicate that diet-induced inhibition of pyruvate dehydrogenase may be an initiating event in decreased oxidation of glucose and increased reliance of the heart on fatty acids for energy production.

52 citations

Journal ArticleDOI
TL;DR: It is concluded that pyruvate oxidation is probably limited by the respiratory chain in state 4 and by the NAD-linked isocitrate dehydrogenase in state 3, and the oxidation of 2-oxoglutarate by swollen mitochondria is also stimulated by high concentrations of ADP and phosphate, and is not uncoupled by arsenate.
Abstract: 1. High rates of state 3 pyruvate oxidation are dependent on high concentrations of inorganic phosphate and a predominance of ADP in the intramitochondrial pool of adenine nucleotides. The latter requirement is most marked at alkaline pH values, where ATP is profoundly inhibitory. 2. Addition of CaCl2 during state 4, state 3 (Chance & Williams, 1955) or uncoupled pyruvate oxidation causes a marked inhibition in the rate of oxygen uptake when low concentrations of mitochondria are employed, but may lead to an enhancement of state 4 oxygen uptake when very high concentrations of mitochondria are used. 3. These properties are consistent with the kinetics of the NAD-linked isocitrate dehydrogenase (EC 1.1.1.41) from this tissue, which is activated by isocitrate, citrate, ADP, phosphate and H+ ions, and inhibited by ATP, NADH and Ca2+. 4. Studies of the redox state of NAD and cytochrome c show that addition of ADP during pyruvate oxidation causes a slight reduction, whereas addition during glycerol phosphate oxidation causes a `classical' oxidation. Nevertheless, it is concluded that pyruvate oxidation is probably limited by the respiratory chain in state 4 and by the NAD-linked isocitrate dehydrogenase in state 3. 5. The oxidation of 2-oxoglutarate by swollen mitochondria is also stimulated by high concentrations of ADP and phosphate, and is not uncoupled by arsenate.

52 citations

Journal ArticleDOI
TL;DR: Determination of the relative configurations and diastereoisomeric purities of the samples of glycerol phosphorothioate demonstrates that all three phosphokinases transfer the thiophosphoryl group with complete stereospecificity, and further shows that these reactions follow an identical stereochemical course.
Abstract: The 2-[18O]phosphorothioate of D-glycerate, chiral at phosphorus, was prepared. The chiral phosphoryl group was transferred enzymically to ADP [by using enolase and pyruvate kinase (ATP:pyruvate 2-O-phosphotransferase; EC 2.7.1.40)] resulting in the synthesis of adenosine 5'-O-([gamma-18O],gamma-thio)triphosphate. This labeled ATP was used as a thiophosphoryl group donor in the reactions catalyzed by glycerol kinase (ATP:glycerol 3-phosphotransferase; EC 2.7.1.30) and by hexokinase (ATP:D-hexose 6-phosphotransferase; EC 2.7.1.1). The product from the latter (glucose 6-phosphorothioate) was converted enzymically into glycerol phosphorothioate. Determination of the relative configurations and diastereoisomeric purities of the samples of glycerol phosphorothioate demonstrates that all three phosphokinases (pyruvate kinase, glycerol kinase, and hexokinase) transfer the thiophosphoryl group with complete stereospecificity, and further shows that these reactions follow an identical stereochemical course.

52 citations

Journal ArticleDOI
TL;DR: The variety of products formed using pyruvate as the sole substrate and the existence of anaplerotic sequences and anabolic pathways which employ pyruVate showed the important role of this metabolite in the energy and biosynthesis metabolism of Campylobacter spp.

52 citations


Network Information
Related Topics (5)
Mitochondrion
51.5K papers, 3M citations
87% related
Protein kinase A
68.4K papers, 3.9M citations
86% related
Phosphorylation
69.3K papers, 3.8M citations
85% related
Endoplasmic reticulum
48.3K papers, 2.4M citations
84% related
Intracellular
41.4K papers, 1.8M citations
84% related
Performance
Metrics
No. of papers in the topic in previous years
YearPapers
202329
202234
202161
202063
201959
201851