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: Since previous studies demonstrated an increase in steady state glyceraldehyde-3-phosphate dehydrogenase RNA during low Oz exposure it is concluded that the level of this RNA is regulated post transcriptionally whereas the other four glycolytic enzyme RNAs are regulated at least partially at thelevel of transcription by oxygen availability.
Abstract: Cytoplasmic β-actin and five glycolytic enzyme cDNAs were isolated from a rat skeletal muscle cDNA library and together with a genomic clone of rat cytochrome c were used as probes to quantitate the respective RNA transcription rates in isolated nuclei run off transcription assays from stationary cells cultured under normal or 2% oxygen. The transcription rates of lactate dehydrogenase, pyruvate kinase, triosephosphate isomerase and aldolase increased by 2–5 fold during the 72 hr exposure to 2% oxygen. There was a small increase in actin RNA transcription while both cytochrome c and glyceraldehyde-3-phosphate dehydrogenase RNA transcription rates decreased. Since previous studies demonstrated an increase in steady state glyceraldehyde-3-phosphate dehydrogenase RNA during low Oz exposure it is concluded that the level of this RNA is regulated post transcriptionally whereas the other four glycolytic enzyme RNAs are regulated at least partially at the level of transcription by oxygen availability. The relative transcriptional rates of the RNAs in this study are related to their cellular RNA and protein concentrations.
97 citations
97 citations
TL;DR: Starvation or induction of alloxan-diabetes had no effect on the total activity of PDH complex in skeletal-muscle mitochondria, but each decreased the concentration of active complex in mitochondria oxidizing 2-oxoglutarate/L-malate and increased the concentrations of Ca2+, pyruvate or dichloracetate required for half-maximal reactivation.
Abstract: The total activity of pyruvate dehydrogenase (PDH) complex in rat hind-limb muscle mitochondria was 76.4 units/g of mitochondrial protein. The proportion of complex in the active form was 34% (as isolated), 8-14% (incubation with respiratory substrates) and greater than 98% (incubation without respiratory substrates). Complex was also inactivated by ATP in the presence of oligomycin B and carbonyl cyanide m-chlorophenylhydrazone. Ca2+ (which activates PDH phosphatase) and pyruvate or dichloroacetate (which inhibit PDH kinase) each increased the concentration of active PDH complex in a concentration-dependent manner in mitochondria oxidizing 2-oxoglutarate/L-malate. Values giving half-maximal activation were 10 nM-Ca2+, 3 mM-pyruvate and 16 microM-dichloroacetate. Activation by Ca2+ was inhibited by Na+ and Mg2+. Mitochondria incubated with [32P]Pi/2-oxoglutarate/L-malate incorporated 32P into three phosphorylation sites in the alpha-chain of PDH; relative rates of phosphorylation were sites 1 greater than 2 greater than 3, and of dephosphorylation, sites 2 greater than 1 greater than 3. Starvation ( 48h ) or induction of alloxan-diabetes had no effect on the total activity of PDH complex in skeletal-muscle mitochondria, but each decreased the concentration of active complex in mitochondria oxidizing 2-oxoglutarate/L-malate and increased the concentrations of Ca2+, pyruvate or dichloracetate required for half-maximal reactivation. In extracts of mitochondria the activity of PDH kinase was increased 2-3-fold by 48 h starvation or alloxan-diabetes, but the activity of PDH phosphatase was unchanged.
96 citations
TL;DR: Overexpression of the M2 isoform of pyruvate kinase protein fused with a nuclear localization signal enhanced cell proliferation in the absence of interleukin-3, suggesting that the nuclear pyruvent kinase plays an important role in cell proliferation.
96 citations
TL;DR: It is concluded that pyruvate carboxylase is an important anaplerotic enzyme in skeletal muscle mitochondria and in relation to the regulation of the level of citric acid cycle intermediates in muscle tissues.
Abstract: Oxygen uptake in skeletal muscle mitochondria respiring on pyruvate or on acetylcarnitine plus propionylcarnitine is stimulated 3--4-fold by bicarbonate. The stimulation is highly dependent on ATP. The respiration rate obtained amounts to 1/4-1/3 of the rate obtained with pyruvate-malate in the presence of ADP. With decreasing ATP/ADP ratios in the medium, a decreasing stimulation by bicarbonate is obtained. Similar results were obtained with heart mitochondria. With ATP added, a pyruvate-dependent build up of citric acid cycle intermediates takes place in incubations with skeletal muscle mitochondria amounting to about 0.5 nmol x min-1 x mg protein-1. In 14CO2-fixation experiments, the activity of pyruvate carboxylase (EC 6.4.2.1) amounts to about 3 nmol x min-1 x mg protein-1 under similar conditions. With propionylcarnitine plus acetylcarnitine a similar stimulation of respiration and fixation of bicarbonate is observed. In this case the respiration and the propionyl-CoA carboxylase (EC 6.4.1.3) is less inhibited by ADP. The results are discussed in relation to the regulation of the level of citric acid cycle intermediates in muscle tissues. It is concluded that pyruvate carboxylase is an important anaplerotic enzyme in skeletal muscle mitochondria.
96 citations