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Pyruvate dehydrogenase

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https://www.readbyqxmd.com/read/28106547/phenotype-dependent-interactions-between-n-acetyl-l-aspartate-and-acetyl-coa-in-septal-sn56-cholinergic-cells-exposed-to-an-excess-of-zinc
#1
Marlena Zyśk, Hanna Bielarczyk, Sylwia Gul-Hinc, Aleksandra Dyś, Beata Gapys, Anna Ronowska, Monika Sakowicz-Burkiewicz, Andrzej Szutowicz
Pyruvate dehydrogenase reaction utilizing glucose-derived pyruvate is an almost exclusive source of acetyl-CoA in different cell mitochondrial compartments of the brain. In neuronal mitochondria, the largest fraction of acetyl-CoA is utilized for energy production and the much smaller one for N-acetyl-L-aspartate (NAA) synthesis. Cholinergic neurons, unlike others, require additional amounts of acetyl-CoA for acetylcholine synthesis. Therefore, several neurotoxic signals, which inhibit pyruvate dehydrogenase, generate deeper shortages of acetyl-CoA and greater mortality of cholinergic neurons than noncholinergic ones...
January 20, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28106122/comparative-genomics-and-transcriptome-analysis-of-aspergillus-niger-and-metabolic-engineering-for-citrate-production
#2
Xian Yin, Hyun-Dong Shin, Jianghua Li, Guocheng Du, Long Liu, Jian Chen
Despite a long and successful history of citrate production in Aspergillus niger, the molecular mechanism of citrate accumulation is only partially understood. In this study, we used comparative genomics and transcriptome analysis of citrate-producing strains-namely, A. niger H915-1 (citrate titer: 157 g L(-1)), A1 (117 g L(-1)), and L2 (76 g L(-1))-to gain a genome-wide view of the mechanism of citrate accumulation. Compared with A. niger A1 and L2, A. niger H915-1 contained 92 mutated genes, including a succinate-semialdehyde dehydrogenase in the γ-aminobutyric acid shunt pathway and an aconitase family protein involved in citrate synthesis...
January 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28101805/ketogenic-diet-in-pyruvate-dehydrogenase-complex-deficiency-short-and-long-term-outcomes
#3
Kalliopi Sofou, Maria Dahlin, Tove Hallböök, Marie Lindefeldt, Gerd Viggedal, Niklas Darin
OBJECTIVES: Our aime was to study the short- and long-term effects of ketogenic diet on the disease course and disease-related outcomes in patients with pyruvate dehydrogenase complex deficiency, the metabolic factors implicated in treatment outcomes, and potential safety and compliance issues. METHODS: Pediatric patients diagnosed with pyruvate dehydrogenase complex deficiency in Sweden and treated with ketogenic diet were evaluated. Study assessments at specific time points included developmental and neurocognitive testing, patient log books, and investigator and parental questionnaires...
January 18, 2017: Journal of Inherited Metabolic Disease
https://www.readbyqxmd.com/read/28100303/ethanol-glycogen-and-glucosylglycerol-represent-competing-carbon-pools-in-ethanol-producing-cells-of-synechocystis-sp-pcc-6803-under-high-salt-conditions
#4
Nadin Pade, Stefan Mikkat, Martin Hagemann
Cyanobacteria are photoautotrophic microorganisms, which are increasingly being used as microbial cell factories to produce for example ethanol directly from solar energy and CO2. Here we analyzed the effects of different salt concentrations on an ethanol-producing strain of Synechocystis sp. PCC 6803 that over-expresses the pyruvate decarboxylase (pdc) from Zymomonas mobilis and the native alcohol dehydrogenase (adhA). Moderate salinities of 2% NaCl had no negative impact on ethanol production, whereas the addition of 4% NaCl resulted in significantly decreased ethanol yields compared to low salt conditions...
January 18, 2017: Microbiology
https://www.readbyqxmd.com/read/28099503/3d-functional-corneal-stromal-tissue-equivalent-based-on-corneal-stromal-stem-cells-and-multi-layered-silk-film-architecture
#5
Chiara E Ghezzi, Benedetto Marelli, Fiorenzo G Omenetto, James L Funderburgh, David L Kaplan
The worldwide need for human cornea equivalents continues to grow. Few clinical options are limited to allogenic and synthetic material replacements. We hypothesized that tissue engineered human cornea systems based on mechanically robust, patterned, porous, thin, optically clear silk protein films, in combination with human corneal stromal stem cells (hCSSCs), would generate 3D functional corneal stroma tissue equivalents, in comparison to previously developed 2D approaches. Silk film contact guidance was used to control the alignment and distribution of hCSSCs on RGD-treated single porous silk films, which were then stacked in an orthogonally, multi-layered architecture and cultured for 9 weeks...
2017: PloS One
https://www.readbyqxmd.com/read/28098952/solving-the-puzzle-of-one-carbon-loss-in-ripostatin-biosynthesis
#6
Chengzhang Fu, David Auerbach, Yanyan Li, Ullrich Scheid, Eva Luxenburger, Ronald Garcia, Herbert Irschik, Rolf Müller
Ripostatin is a promising antibiotic that inhibits RNA polymerase by binding to a novel binding site. In this study, the characterization of the biosynthetic gene cluster of ripostatin, which is a peculiar polyketide synthase (PKS) hybrid cluster encoding cis- and trans-acyltransferase PKS genes, is reported. Moreover, an unprecedented mechanism for phenyl acetic acid formation and loading as a starter unit was discovered. This phenyl-C2 unit is derived from phenylpyruvate (phenyl-C3) and the mechanism described herein explains the mysterious loss of one carbon atom in ripostatin biosynthesis from the phenyl-C3 precursor...
January 18, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28094552/glucose-metabolism-in-cancer-and-ischemia-possible-therapeutic-consequences-of-the-warburg-effect
#7
Spela Salamon, Eva Podbregar, Peter Kubatka, Dietrich Büsselberg, Martin Caprnda, Radka Opatrilova, Vanda Valentova, Mariusz Adamek, Peter Kruzliak, Matej Podbregar
The Warburg effect states that the main source of energy for cancer cells is not aerobic respiration, but glycolysis-even in normoxia. The shift from one to the other is governed by mutually counteracting enzymes: pyruvate dehydrogenase and pyruvate dehydrogenase kinase (PDK). Anaerobic metabolism of cancer cells promotes cell proliferation, local tissue immunosuppression, resistance to hypoxic conditions, and metastatic processes. By switching glucose back to oxidative metabolism, these effects might be reversed...
January 17, 2017: Nutrition and Cancer
https://www.readbyqxmd.com/read/28087461/low-glucose-stress-decreases-cellular-nadh-and-mitochondrial-atp-in-colonic-epithelial-cancer-cells-influence-of-mitochondrial-substrates
#8
Magdalena L Circu, Ronald E Maloney, Tak Yee Aw
In this study, we investigated how colonic epithelial cells maintained pyridine nucleotide (NADH/NAD(+)) redox homeostasis upon acute metabolic variation imposed by glucose deprivation or supplementation with mitochondrial substrates, succinate and malate/glutamate (M/G). Our results showed that low glucose caused cellular NADH/NAD(+) redox imbalance that diminished lactate dehydrogenase (LDH) activity and resulted in lower lactate contents. The concurrent activation of malic enzyme (ME) suggested a role for malate in preserving cellular pyruvate that remained unchanged at low glucose...
January 10, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28080041/in-vitro-reconstitution-and-optimization-of-the-entire-pathway-to-convert-glucose-into-fatty-acid
#9
Zheng Liu, Yuchen Zhang, Xiaoge Jia, Mengzhu Hu, Zixin Deng, Yancheng Xu, Tiangang Liu
Glucose and fatty acids play essential physiological roles in nearly all living organisms and the pathway that converts glucose into fatty acid is pivotal to the central metabolic network. We have successfully reconstituted a pathway that converts glucose to fatty acid in vitro using 30 purified proteins. Through systematic titration and optimization of the glycolytic pathway and pyruvate dehydrogenase, we increased the yield of free fatty acid from non-detectable to a level that exceeded 9% of the theoretical yield...
January 12, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28076853/pyruvate-dehydrogenase-expression-is-negatively-associated-with-cell-stemness-and-worse-clinical-outcome-in-prostate-cancers
#10
Yali Zhong, Xiaoli Li, Yasai Ji, Xiaoran Li, Yaqing Li, Dandan Yu, Yuan Yuan, Jian Liu, Huixiang Li, Mingzhi Zhang, Zhenyu Ji, Dandan Fan, Jianguo Wen, Mariusz Adam Goscinski, Long Yuan, Bin Hao, Jahn M Nesland, Zhenhe Suo
Cells generate adenosine-5'-triphosphate (ATP), the major currency for energy-consuming reactions, through mitochondrial oxidative phosphorylation (OXPHOS) and glycolysis. One of the remarkable features of cancer cells is aerobic glycolysis, also known as the "Warburg Effect", in which cancer cells rely preferentially on glycolysis instead of mitochondrial OXPHOS as the main energy source even in the presence of high oxygen tension. One of the main players in controlling OXPHOS is the mitochondrial gatekeeperpyruvate dehydrogenase complex (PDHc) and its major subunit is E1α (PDHA1)...
January 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28070562/biological-and-chemical-adaptation-to-endogenous-hydrogen-peroxide-production-in-streptococcus-pneumoniae-d39
#11
John P Lisher, Ho-Ching Tiffany Tsui, Smirla Ramos-Montañez, Kristy L Hentchel, Julia E Martin, Jonathan C Trinidad, Malcolm E Winkler, David P Giedroc
The catalase-negative, facultative anaerobe Streptococcus pneumoniae D39 is naturally resistant to hydrogen peroxide (H2O2) produced endogenously by pyruvate oxidase (SpxB). Here, we investigate the adaptive response to endogenously produced H2O2. We show that lactate oxidase, which converts lactate to pyruvate, positively impacts pyruvate flux through SpxB and that ΔlctO mutants produce significantly lower H2O2. In addition, both the SpxB pathway and a candidate pyruvate dehydrogenase complex (PDHC) pathway contribute to acetyl coenzyme A (acetyl-CoA) production during aerobic growth, and the pyruvate format lyase (PFL) pathway is the major acetyl-CoA pathway during anaerobic growth...
January 2017: MSphere
https://www.readbyqxmd.com/read/28069660/antioxidant-treatment-attenuates-lactate-production-in-diabetic-nephropathy
#12
Christoffer Laustsen, Per Mose Nielsen, Thomas Stokholm Nørlinger, Haiyun Qi, Uffe Kjærgaard Pedersen, Lotte Bonde Bertelsen, Jakob Appel Østergaard, Allan Flyvbjerg, Jan Henrik Ardenkjær-Larsen, Fredrik Palm, Hans Stødkilde-Jørgensen
The early progression of diabetic nephropathy is notoriously difficult to detect and quantify before the occurrence of substantial histological damage. Recently, hyperpolarized [1-(13)C]pyruvate has demonstrated increased lactate production in the kidney early after the onset of diabetes, implying increased lactate dehydrogenase activity as a consequence of increased nicotinamide adenine dinucleotide substrate availability due to upregulation of the polyol pathway, i.e., pseudohypoxia. In this study, we investigated the role of oxidative stress in mediating these metabolic alterations using state-of-the-art hyperpolarized magnetic resonance (MR) imaging...
January 1, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28068366/overproduction-of-%C3%AE-lipoic-acid-by-gene-manipulated-escherichia-coli
#13
Yirong Sun, Wenbin Zhang, Jincheng Ma, Hongshen Pang, Haihong Wang
Alpha-lipoic acid (LA) is an important enzyme cofactor widely used by organisms and is also a natural antioxidant for the treatment of pathologies driven by low levels of endogenous antioxidants. In order to establish a safer and more efficient process for LA production, we developed a new biological method for LA synthesis based on the emerging knowledge of lipoic acid biosynthesis. We first cloned the lipD gene, which encodes the lipoyl domain of the E2 subunit of pyruvate dehydrogenase, allowing high levels of LipD production...
2017: PloS One
https://www.readbyqxmd.com/read/28063005/albendazole-inhibits-hif-1%C3%AE-dependent-glycolysis-and-vegf-expression-in-non-small-cell-lung-cancer-cells
#14
Fang Zhou, Jin Du, Jianjun Wang
Albendazole (ABZ) has an anti-tumor ability and inhibits HIF-1α activity. HIF-1α is associated with glycolysis and vascular endothelial cell growth factor (VEGF) expression, which plays an important role in cancer progression. These clues indicate that ABZ exerts an anti-cancer effect by regulating glycolysis and VEGF expression. The aim of this study is to clarify the effects of ABZ on non-small cell lung cancer (NSCLC) cells and explore the underlying molecular mechanisms. The expression levels of HIF-1α and VEGF were detected using western blot analysis, and the effect of ABZ on glycolysis was evaluated by measuring the relative activities of hexokinase (HK), pyruvate kinase (PK), and lactate dehydrogenase (LDH) and detecting the production of lactate in A549 and H1299 cells...
January 7, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28060330/hyperpolarized-13c-metabolic-magnetic-resonance-spectroscopy-and-imaging
#15
Eugen Kubala, Kim A Muñoz-Álvarez, Geoffrey Topping, Christian Hundshammer, Benedikt Feuerecker, Pedro A Gómez, Giorgio Pariani, Franz Schilling, Steffen J Glaser, Rolf F Schulte, Marion I Menzel, Markus Schwaiger
In the past decades, new methods for tumor staging, restaging, treatment response monitoring, and recurrence detection of a variety of cancers have emerged in conjunction with the state-of-the-art positron emission tomography with (18)F-fluorodeoxyglucose ([(18)F]-FDG PET). (13)C magnetic resonance spectroscopic imaging ((13)CMRSI) is a minimally invasive imaging method that enables the monitoring of metabolism in vivo and in real time. As with any other method based on (13)C nuclear magnetic resonance (NMR), it faces the challenge of low thermal polarization and a subsequent low signal-to-noise ratio due to the relatively low gyromagnetic ratio of (13)C and its low natural abundance in biological samples...
December 30, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28054837/radiosurgery-alters-the-endothelial-surface-proteome-externalized-intracellular-molecules-as-potential-vascular-targets-in-irradiated-brain-arteriovenous-malformations
#16
Lucinda S McRobb, Vivienne S Lee, Margaret Simonian, Zhenjun Zhao, Santhosh George Thomas, Markus Wiedmann, Jude V Amal Raj, Michael Grace, Vaughan Moutrie, Matthew J McKay, Mark P Molloy, Marcus A Stoodley
Stereotactic radiosurgery (SRS) is an established treatment for brain arteriovenous malformations (AVMs) that drives blood vessel closure through cellular proliferation, thrombosis and fibrosis, but is limited by a delay to occlusion of 2-3 years and a maximum treatable size of 3 cm. In this current study we used SRS as a priming tool to elicit novel protein expression on the endothelium of irradiated AVM vessels, and these proteins were then targeted with prothrombotic conjugates to induce rapid thrombosis and vessel closure...
January 5, 2017: Radiation Research
https://www.readbyqxmd.com/read/28049038/trimethylamine-n-oxide-impairs-pyruvate-and-fatty-acid-oxidation-in-cardiac-mitochondria
#17
Marina Makrecka-Kuka, Kristine Volska, Unigunde Antone, Reinis Vilskersts, Solveiga Grinberga, Dace Bandere, Edgars Liepinsh, Maija Dambrova
Increased plasma concentration of trimethylamine N-oxide (TMAO), a proatherogenic metabolite, has been linked to adverse cardiovascular outcomes; however, it remains unclear whether TMAO is a biomarker or whether it induces direct detrimental cardiovascular effects. Because altered cardiac energy metabolism and mitochondrial dysfunction play crucial roles in the development of cardiovascular diseases, we hypothesized that increased TMAO concentration may alter mitochondrial energy metabolism. The aim of the present study was to determine the effects of TMAO on cardiac mitochondrial energy metabolism...
December 31, 2016: Toxicology Letters
https://www.readbyqxmd.com/read/28046118/transcriptome-analysis-identifies-key-metabolic-changes-in-the-hooded-seal-cystophora-cristata-brain-in-response-to-hypoxia-and-reoxygenation
#18
Mariana Leivas Müller Hoff, Andrej Fabrizius, Nicole U Czech-Damal, Lars P Folkow, Thorsten Burmester
The brain of diving mammals tolerates low oxygen conditions better than the brain of most terrestrial mammals. Previously, it has been demonstrated that the neurons in brain slices of the hooded seal (Cystophora cristata) withstand hypoxia longer than those of mouse, and also tolerate reduced glucose supply and high lactate concentrations. This tolerance appears to be accompanied by a shift in the oxidative energy metabolism to the astrocytes in the seal while in terrestrial mammals the aerobic energy production mainly takes place in neurons...
2017: PloS One
https://www.readbyqxmd.com/read/28043922/reconstruction-of-a-genome-scale-metabolic-model-and-in-silico-analysis-of-the-polymalic-acid-producer-aureobasidium-pullulans-cctcc-m2012223
#19
Jun Feng, Jing Yang, Xiaorong Li, Meijin Guo, Bochu Wang, Shang-Tian Yang, Xiang Zou
Aureobasidium pullulans is a yeast-like fungus used for producing biopolymers e.g. polymalic acid (PMA) and pullulan. A high PMA producing strain, A. pullulans CCTCC M2012223, was isolated and sequenced in our previous study. To understand its metabolic performance, a genome-scale metabolic model, iZX637, consisting of 637 genes, 1347 reactions and 1133 metabolites, was reconstructed based on genome annotation and literature mining studies. The iZX637 model was validated by simulating cell growth, utilization of carbon and nitrogen sources, and gene essentiality analysis in A...
December 30, 2016: Gene
https://www.readbyqxmd.com/read/28040265/pyruvate-dehydrogenase-kinase-4-deficiency-attenuates-cisplatin-induced-acute-kidney-injury
#20
Chang Joo Oh, Chae-Myeong Ha, Young-Keun Choi, Sungmi Park, Mi Sun Choe, Nam Ho Jeoung, Yang Hoon Huh, Hyo-Jeong Kim, Hee-Seok Kweon, Ji-Min Lee, Sun Joo Lee, Jae-Han Jeon, Robert A Harris, Keun-Gyu Park, In-Kyu Lee
Clinical prescription of cisplatin, one of the most widely used chemotherapeutic agents, is limited by its side effects, particularly tubular injury-associated nephrotoxicity. Since details of the underlying mechanisms are not fully understood, we investigated the role of pyruvate dehydrogenase kinase (PDK) in cisplatin-induced acute kidney injury. Among the PDK isoforms, PDK4 mRNA and protein levels were markedly increased in the kidneys of mice treated with cisplatin, and c-Jun N-terminal kinase activation was involved in cisplatin-induced renal PDK4 expression...
December 28, 2016: Kidney International
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