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
TL;DR: The results suggest that the acetylation of PDHA1 provides another layer of enzymatic regulation, in addition to phosphorylation, involving a reversible acetyllysine, suggesting that theacetylome, as well as the kinome, links glycolysis to respiration.

148 citations

Journal ArticleDOI
TL;DR: Corynebacterium glutamicum was engineered for the production of l-valine from glucose by deletion of the aceE gene encoding the E1p enzyme of the pyruvate dehydrogenase complex and additional overexpression of the ilvBNCE genes encoding the l-Valine biosynthetic enzymes acetohydroxyacid synthase, isomeroreductase, and transaminase B.
Abstract: Corynebacterium glutamicum was engineered for the production of L-valine from glucose by deletion of the aceE gene encoding the E1p enzyme of the pyruvate dehydrogenase complex and additional overexpression of the ilvBNCE genes encoding the L-valine biosynthetic enzymes acetohydroxyacid synthase, isomeroreductase, and transaminase B. In the absence of cellular growth, C. glutamicum DeltaaceE showed a relatively high intracellular concentration of pyruvate (25.9 mM) and produced significant amounts of pyruvate, L-alanine, and L-valine from glucose as the sole carbon source. Lactate or acetate was not formed. Plasmid-bound overexpression of ilvBNCE in C. glutamicum DeltaaceE resulted in an approximately 10-fold-lower intracellular pyruvate concentration (2.3 mM) and a shift of the extracellular product pattern from pyruvate and L-alanine towards L-valine. In fed-batch fermentations at high cell densities and an excess of glucose, C. glutamicum DeltaaceE(pJC4ilvBNCE) produced up to 210 mM L-valine with a volumetric productivity of 10.0 mM h(-1) (1.17 g l(-1) h(-1)) and a maximum yield of about 0.6 mol per mol (0.4 g per g) of glucose.

148 citations

Journal ArticleDOI
TL;DR: 1α,25(OH)2D3 regulates mitochondrial function, dynamics, and enzyme function, which is likely to influence muscle strength and vitamin D deficiency and chronic renal failure in skeletal muscle cells.

147 citations

Book ChapterDOI
TL;DR: This chapter discusses the determination of purification and properties of the pyruvate dehydrogenase complex, and an assay based on colorimetric determination of S -acetyldihydrolipoamide as the ferric acethydroxamate complex.
Abstract: Publisher Summary This chapter discusses the determination of purification and properties of the pyruvate dehydrogenase complex. The Escherichia coli pyruvate dehydrogenase complex has been separated into three enzymes, pyruvate decarboxylase (E 1 ), lipoyl reductasetransacetylase (E 2 ), and dihydrolipoyl dehydrogenase (E 3 ), and has been reconstituted from the isolated enzymes. In the case of dihydrolipoyl dehydrogenase, the assay is based on spectrophotometric determination of the rate of reduced diphosphopyridine nucleotide (DPNH) oxidation (at 340 mμ) in the presence of the dehydrogenase and lipoamide. In the case of pyruvate decarboxylase, the assay is a modification of that described by Hager. It is based on colorimetric determination of ferrocyanide (as Prussian blue) produced by oxidative decarboxylation of pyruvate with ferricyanide as electron acceptor. In the case of lipoyl reductase-transacetylase, the assay is based on colorimetric determination of S -acetyldihydrolipoamide as the ferric acethydroxamate complex. Acetyl CoA is generated from acetyl phosphate in the presence of catalytic amounts of CoA and phosphotransacetylase, and the acetyl group is transferred to dihydrolipoamide in the presence of lipoyl reductase-transacetylase.

146 citations

Journal ArticleDOI
TL;DR: The mechanistic basis for DCA anti‐cancer activity was re‐evaluated in vitro using biochemical, cellular and proteomic approaches and the ability of DCA to target cell lines with defects in the electron transport chain and to synergize with existing chemotherapeutics supports further preclinical development.
Abstract: The "Warburg effect," also termed aerobic glycolysis, describes the increased reliance of cancer cells on glycolysis for ATP production, even in the presence of oxygen. Consequently, there is continued interest in inhibitors of glycolysis as cancer therapeutics. One example is dichloroacetate (DCA), a pyruvate mimetic that stimulates oxidative phosphorylation through inhibition of pyruvate dehydrogenase kinase. In this study, the mechanistic basis for DCA anti-cancer activity was re-evaluated in vitro using biochemical, cellular and proteomic approaches. Results demonstrated that DCA is relatively inactive (IC(50) ≥ 17 mM, 48 hr), induces apoptosis only at high concentrations (≥ 25 mM, 48 hr) and is not cancer cell selective. Subsequent 2D-PAGE proteomic analysis confirmed DCA-induced growth suppression without apoptosis induction. Furthermore, DCA depolarizes mitochondria and promotes reactive oxygen species (ROS) generation in all cell types. However, DCA was found to have selective activity against rho(0) cells [mitochondrial DNA (mtDNA) deficient] and to synergize with 2-deoxyglucose in complex IV deficient HCT116 p53(-/-) cells. DCA also synergized in vitro with cisplatin and topotecan, two antineoplastic agents known to damage mitochondrial DNA. These data suggest that in cells "hardwired" to selectively utilize glycolysis for ATP generation (e.g., through mtDNA mutations), the ability of DCA to force oxidative phosphorylation confers selective toxicity. In conclusion, although we provide a mechanism distinct from that reported previously, the ability of DCA to target cell lines with defects in the electron transport chain and to synergize with existing chemotherapeutics supports further preclinical development.

146 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