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Pyruvate dehydrogenase

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https://www.readbyqxmd.com/read/28432553/cardiolipin-deficiency-causes-triacylglycerol-accumulation-in-saccharomyces-cerevisiae
#1
Pradeep Kumar Yadav, Ram Rajasekharan
In yeast, the synthesis of cardiolipin (CL) and phosphatidylethanolamine (PE) occurs mainly in mitochondria. CL and PE have overlapping functions, and they are required for mitochondrial function. PE is physiologically linked with triacylglycerol (TAG) metabolism in Saccharomyces cerevisiae, involving an acyl-CoA-independent pathway through the phospholipid:diacylglycerol acyltransferase activity of the Lro1 protein. There is no report on the physiological link between CL and TAG metabolism. Here we report a metabolic link between CL and TAG accumulation in the S...
April 21, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28432125/sequential-adaptive-changes-in-a-c-myc-driven-model-of-hepatocellular-carcinoma
#2
James M Dolezal, Huabo Wang, Sucheta Kulkarni, Laura Jackson, Jie Lu, Sarangarajan Ranganathan, Eric S Goetzman, Sivakama Bharathi, Kevin Beezhold, Craig A Byersdorfer, Edward V Prochownik
Hepatocellular carcinoma (HCC) is a common cancer that frequently over-expresses the c-Myc (Myc) oncoprotein. Using a mouse model of Myc-induced HCC, we studied the metabolic, biochemical and molecular changes accompanying HCC progression, regression and recurrence. These involved altered rates of pyruvate and fatty acid β-oxidation and the likely re-directing of glutamine into biosynthetic rather than energy-generating pathways. Initial tumors also showed reduced mitochondrial mass and differential contributions of electron transport chain Complexes I and II to respiration...
April 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28429326/wax-ester-fermentation-and-its-application-for-biofuel-production
#3
Hiroshi Inui, Takahiro Ishikawa, Masahiro Tamoi
In Euglena cells under anaerobic conditions, paramylon, the storage polysaccharide, is promptly degraded and converted to wax esters. The wax esters synthesized are composed of saturated fatty acids and alcohols with chain lengths of 10-18, and the major constituents are myristic acid and myristyl alcohol. Since the anaerobic cells gain ATP through the conversion of paramylon to wax esters, the phenomenon is named "wax ester fermentation". The wax ester fermentation is quite unique in that the end products, i...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28428273/assessing-prostate-cancer-aggressiveness-with-hyperpolarized-dual-agent-3d-dynamic-imaging-of-metabolism-and-perfusion
#4
Hsin-Yu Chen, Peder E Z Larson, Robert A Bok, Cornelius von Morze, Renuka Sriram, Romelyn Delos Santos, Justin Delos Santos, Jeremy W Gordon, Naeim Bahrami, Marcus Ferrone, John Kurhanewicz, Daniel B Vigneron
New magnetic resonance (MR) molecular imaging techniques offer the potential for non-invasive, simultaneous quantification of metabolic and perfusion parameters in tumors. This study applied a 3D dynamic dual-agent hyperpolarized (13)C magnetic resonance spectroscopic imaging (MRSI) approach with (13)C-pyruvate and (13)C-urea to investigate differences in perfusion and metabolism between low and high grade tumors in the TRAMP transgenic mouse model of prostate cancer. Dynamic MR data were corrected for T1 relaxation and RF excitation and modeled to provide quantitative measures of pyruvate to lactate flux (kPL) and urea perfusion (urea AUC) that correlated with TRAMP tumor histologic grade...
April 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28428201/dihydrolipoamide-dehydrogenase-lpd-rv0462-specific-t-cell-recall-responses-are-higher-in-healthy-household-contacts-of-tb-a-novel-immunodominant-antigen-from-m-tuberculosis
#5
Santhi Devasundaram, Alamelu Raja
The partial effectiveness against pulmonary tuberculosis (PTB), displayed by the existing tuberculosis (TB) vaccine, bacillus Calmette-Guérin (BCG), highlights the need for novel vaccines to replace or improve BCG. In TB immunology, antigen-specific cellular immune response is frequently considered indispensable. Latency-associated antigens are intriguing as targets for TB vaccine development. The mycobacterial protein, dihydrolipoamide dehydrogenase (Lpd; Rv0462), the third enzyme of the pyruvate dehydrogenase (PDH) complex, facilitates Mycobacterium tuberculosis to resist host reactive nitrogen intermediates...
April 20, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28427942/inhibitory-effects-of-ethyl-pyruvate-on-platelet-aggregation-and-phosphatidylserine-exposure
#6
Wenjin Li, Xinyu Yang, Minyuan Peng, Can Li, Guangfu Mu, Fangping Chen
Ethyl pyruvate (EP) is a stable lipophilic pyruvate derivative. Studies demonstrated that EP shows potent anti-oxidation, anti-inflammatory and anti-coagulant effects. Inflammation and coagulation are closely interacted with platelet activation. However, it is unclear whether EP has anti-platelet effects. Therefore, we investigated the anti-platelet effect of EP in this study in vitro. We found that EP inhibited agonists induced platelets aggregation, ATP release and adhesion to collagen. Flow cytometric analysis revealed that EP inhibited agonist induced platelets PAC-1 binding, as well as P-selectin and CD40L expression...
April 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28425930/the-peculiar-glycolytic-pathway-in-hyperthermophylic-archaea-understanding-its-whims-by-experimentation-in-silico
#7
Yanfei Zhang, Theresa Kouril, Jacky L Snoep, Bettina Siebers, Matteo Barberis, Hans V Westerhoff
Mathematical models are key to systems biology where they typically describe the topology and dynamics of biological networks, listing biochemical entities and their relationships with one another. Some (hyper)thermophilic Archaea contain an enzyme, called non-phosphorylating glyceraldehyde-3-phosphate dehydrogenase (GAPN), which catalyzes the direct oxidation of glyceraldehyde-3-phosphate to 3-phosphoglycerate omitting adenosine 5'-triphosphate (ATP) formation by substrate-level-phosphorylation via phosphoglycerate kinase...
April 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28424096/metabolic-and-proteomic-analyses-of-product-selectivity-and-redox-regulation-in-clostridium-pasteurianum-grown-on-glycerol-under-varied-iron-availability
#8
Christin Groeger, Wei Wang, Wael Sabra, Tyll Utesch, An-Ping Zeng
BACKGROUND: Clostridium pasteurianum as an emerging new microbial cell factory can produce both n-butanol (BuOH) and 1,3-propanediol (1,3-PDO), and the pattern of product formation changes significantly with the composition of the culture medium. Among others iron content in the medium was shown to strongly affect the products selectivity. However, the mechanism behind this metabolic regulation is still unclear. For a better understanding of such metabolic regulation and for process optimization, we carried out fermentation experiments under either iron excess or iron limitation conditions, and performed metabolic, stoichiometric and proteomic analyses...
April 19, 2017: Microbial Cell Factories
https://www.readbyqxmd.com/read/28421296/metabolite-signatures-of-doxorubicin-induced-toxicity-in-human-induced-pluripotent-stem-cell-derived-cardiomyocytes
#9
Umesh Chaudhari, James K Ellis, Vilas Wagh, Harshal Nemade, Jürgen Hescheler, Hector C Keun, Agapios Sachinidis
Drug-induced off-target cardiotoxicity, particularly following anti-cancer therapy, is a major concern in new drug discovery and development. To ensure patient safety and efficient pharmaceutical drug development, there is an urgent need to develop more predictive cell model systems and distinct toxicity signatures. In this study, we applied our previously proposed repeated exposure toxicity methodology and performed (1)H NMR spectroscopy-based extracellular metabolic profiling in culture medium of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) exposed to doxorubicin (DOX), an anti-cancer agent...
April 18, 2017: Amino Acids
https://www.readbyqxmd.com/read/28419197/inhibition-of-sarcolemmal-fat-cd36-by-sulfo-n-succinimidyl-oleate-rapidly-corrects-metabolism-and-restores-function-in-the-diabetic-heart-following-hypoxia-reoxygenation
#10
Latt S Mansor, Maria da Luz Sousa Fialho, Georgina Yea, Will A Coumans, James A West, Matthew Kerr, Carolyn A Carr, Joost J F P Luiken, Jan F C Glatz, Rhys D Evans, Julian L Griffin, Damian J Tyler, Kieran Clarke, Lisa C Heather
Aims: The type 2 diabetic heart oxidizes more fat and less glucose, which can impair metabolic flexibility and function. Increased sarcolemmal fatty acid translocase (FAT/CD36) imports more fatty acid into the diabetic myocardium, feeding increased fatty acid oxidation and elevated lipid deposition. Unlike other metabolic modulators that target mitochondrial fatty acid oxidation, we proposed that pharmacologically inhibiting fatty acid uptake, as the primary step in the pathway, would provide an alternative mechanism to rebalance metabolism and prevent lipid accumulation following hypoxic stress...
April 17, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28418108/metabolic-characterization-and-transformation-of-the-non-dairy-lactococcus-lactis-strain-kf147-for-production-of-ethanol-from-xylose
#11
Kia Vest Petersen, Jianming Liu, Jun Chen, Jan Martinussen, Peter Ruhdal Jensen, Christian Solem
The non-dairy lactic acid bacterium Lactococcus lactis KF147 can utilize xylose as the sole energy source. To assess whether KF147 could serve as a platform organism for converting second generation sugars into useful chemicals, we characterized growth and product formation for KF147 when grown on xylose. In a defined medium KF147 was found to co-metabolize xylose and arginine, resulting in bi-phasic growth. Especially at low xylose concentrations, arginine significantly improved growth rate. To facilitate further studies of the xylose metabolism, we eliminated arginine catabolism by deleting the arcA gene encoding the arginine deiminase...
April 18, 2017: Biotechnology Journal
https://www.readbyqxmd.com/read/28414314/cell-competition-with-normal-epithelial-cells-promotes-apical-extrusion-of-transformed-cells-through-metabolic%C3%A2-changes
#12
Shunsuke Kon, Kojiro Ishibashi, Hiroto Katoh, Sho Kitamoto, Takanobu Shirai, Shinya Tanaka, Mihoko Kajita, Susumu Ishikawa, Hajime Yamauchi, Yuta Yako, Tomoko Kamasaki, Tomohiro Matsumoto, Hirotaka Watanabe, Riku Egami, Ayana Sasaki, Atsuko Nishikawa, Ikumi Kameda, Takeshi Maruyama, Rika Narumi, Tomoko Morita, Yoshiteru Sasaki, Ryosuke Enoki, Sato Honma, Hiromi Imamura, Masanobu Oshima, Tomoyoshi Soga, Jun-Ichi Miyazaki, Michael R Duchen, Jin-Min Nam, Yasuhito Onodera, Shingo Yoshioka, Junichi Kikuta, Masaru Ishii, Masamichi Imajo, Eisuke Nishida, Yoichiro Fujioka, Yusuke Ohba, Toshiro Sato, Yasuyuki Fujita
Recent studies have revealed that newly emerging transformed cells are often apically extruded from epithelial tissues. During this process, normal epithelial cells can recognize and actively eliminate transformed cells, a process called epithelial defence against cancer (EDAC). Here, we show that mitochondrial membrane potential is diminished in RasV12-transformed cells when they are surrounded by normal cells. In addition, glucose uptake is elevated, leading to higher lactate production. The mitochondrial dysfunction is driven by upregulation of pyruvate dehydrogenase kinase 4 (PDK4), which positively regulates elimination of RasV12-transformed cells...
April 17, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28410193/metabolic-targeting-of-egfrviii-pdk1-axis-in-temozolomide-resistant-glioblastoma
#13
Kiran K Velpula, Maheedhara R Guda, Kamlesh Sahu, Jack Tuszynski, Swapna Asuthkar, Sarah E Bach, Justin D Lathia, Andrew J Tsung
Glioblastomas are characterized by amplification of EGFR. Approximately half of tumors with EGFR over-expression also express a constitutively active ligand independent EGFR variant III (EGFRvIII). While current treatments emphasize surgery followed by radiation and chemotherapy with Temozolomide (TMZ), acquired chemoresistance is a universal feature of recurrent GBMs. To mimic the GBM resistant state, we generated an in vitro TMZ resistant model and demonstrated that dichloroacetate (DCA), a metabolic inhibitor of pyruvate dehydrogenase kinase 1 (PDK1), reverses the Warburg effect...
March 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28410146/nok-mediates-glycolysis-and-nuclear-pdc-associated-histone-acetylation
#14
Wei-Ye Shi, Xiao Yang, Bo Huang, Wen H Shen, Li Liu
NOK is a potent oncogene that can transform normal cells to cancer cells. We hypothesized that NOK might impact cancer cell metabolism and histone acetylation. We show that NOK localizes in the mitochondria, and while it minimally impacts tricarboxylic acid (TCA) cycle, it markedly inhibits the process of electron transport and oxidative phosphorylation processes and dramatically enhances aerobic glycolysis in cancer cells. NOK promotes the mitochondrial-nuclear translocation of pyruvate dehydrogenase complex (PDC), and enhances histone acetylation in the nucleus...
June 1, 2017: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/28405929/thermodynamics-in-cancers-opposing-interactions-between-ppar-gamma-and-the-canonical-wnt-beta-catenin-pathway
#15
REVIEW
Yves Lecarpentier, Victor Claes, Alexandre Vallée, Jean-Louis Hébert
Cancer cells are the site of numerous metabolic and thermodynamic abnormalities. We focus this review on the interactions between the canonical WNT/beta-catenin pathway and peroxisome proliferator-activated receptor gamma (PPAR gamma) in cancers and their implications from an energetic and metabolic point of view. In numerous tissues, PPAR gamma activation induces inhibition of beta-catenin pathway, while the activation of the canonical WNT/beta-catenin pathway inactivates PPAR gamma. In most cancers but not all, PPAR gamma is downregulated while the WNT/beta-catenin pathway is upregulated...
December 2017: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/28404377/h2s-induced-s-sulfhydration-of-lactate-dehydrogenase-a-ldha-stimulates-cellular-bioenergetics-in-hct116-colon-cancer-cells
#16
Ashley A Untereiner, Gabor Oláh, Katalin Módis, Mark R Hellmich, Csaba Szabo
Cystathionine-β-synthase (CBS) is upregulated and hydrogen sulfide (H2S) production is increased in colon cancer cells. The functional consequence of this response is stimulation of cellular bioenergetics and tumor growth and proliferation. Lactate dehydrogenase A (LDHA) is also upregulated in various colon cancer cells and has been previously implicated in tumor cell bioenergetics and proliferation. In the present study, we sought to determine the potential interaction between the H2S pathway and LDH activity in the control of bioenergetics and proliferation of colon cancer, using the colon cancer line HCT116...
April 9, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28400503/pgc-1%C3%AE-and-fasting-induced-pdh-regulation-in-mouse-skeletal-muscle
#17
Anders Gudiksen, Henriette Pilegaard
The purpose of the present study was to examine whether lack of skeletal muscle peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) affects the switch in substrate utilization from a fed to fasted state and the fasting-induced pyruvate dehydrogenase (PDH) regulation in skeletal muscle. Skeletal muscle-specific PGC-1α knockout (MKO) mice and floxed littermate controls were fed or fasted for 24 h. Fasting reduced PDHa activity, increased phosphorylation of all four known sites on PDH-E1α and increased pyruvate dehydrogenase kinase (PDK4) and sirtuin 3 (SIRT3) protein levels, but did not alter total acetylation of PDH-E1α Lack of muscle PGC-1α did not affect the switch from glucose to fat oxidation in the transition from the fed to fasted state, but was associated with lower and higher respiratory exchange ratio (RER) in the fed and fasted state, respectively...
April 2017: Physiological Reports
https://www.readbyqxmd.com/read/28400330/metabolomics-driven-approach-to-solving-a-coa-imbalance-for-improved-1-butanol-production-in-escherichia-coli
#18
Toshiyuki Ohtake, Sammy Pontrelli, Walter A Laviña, James C Liao, Sastia P Putri, Eiichiro Fukusaki
High titer 1-butanol production in Escherichia coli has previously been achieved by overexpression of a modified clostridial 1-butanol production pathway and subsequent deletion of native fermentation pathways. This strategy couples growth with production as 1-butanol pathway offers the only available terminal electron acceptors required for growth in anaerobic conditions. With further inclusion of other well-established metabolic engineering principles, a titer of 15g/L has been obtained. In achieving this titer, many currently existing strategies have been exhausted, and 1-butanol toxicity level has been surpassed...
April 8, 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/28391608/mechanistic-analysis-of-fluorescence-quenching-of-reduced-nicotinamide-adenine-dinucleotide-by-oxamate-in-lactate-dehydrogenase-ternary-complexes
#19
Huo-Lei Peng, Robert Callender
Fluorescence of Reduced Nicotinamide Adenine Dinucleotide (NADH) is extensively employed in studies of oxidoreductases. A substantial amount of static and kinetic work has focused on the binding of pyruvate or substrate mimic oxamate to LDH•NADH where substantial fluorescence quenching is typically observed. However, the quenching mechanism is not well understood limiting structural interpretation. Based on time-dependent density functional theory (TDDFT) computations with cam-B3LYP functional in conjunction with the analysis of previous experimental results, we propose that bound oxamate acts as an electron acceptor in the quenching of fluorescence of NADH in the ternary complex, where a charge transfer (CT) state characterized by excitation from the highest occupied molecular orbital (HOMO) of the nicotinamide moiety of NADH to the lowest unoccupied molecular orbital (LUMO) of oxamate exists close to the locally excited (LE) state involving only the nicotinamide moiety...
April 9, 2017: Photochemistry and Photobiology
https://www.readbyqxmd.com/read/28387439/oncophosphosignaling-favors-a-glycolytic-phenotype-in-human-drug-resistant-leukemia
#20
Alessandra V S Faria, Thaís F Tornatore, Renato Milani, Karla C S Queiroz, Igor H Sampaio, Emanuella M B Fonseca, Karin J P Rocha-Brito, Tamira Oliveira Santos, Leonardo R Silveira, Maikel P Peppelenbosch, Carmen Veríssima Ferreira-Halder
In chemoresistant leukemia cells (Lucena-1), the low molecular weight protein tyrosine phosphatase (LMWPTP) is about 20-fold more active than in their susceptible counterpart (K562). We found this phosphatase ensures the activated statuses of Src and Bcr-Abl. Since phosphorylation and dephosphorylation of proteins represent a key post-translational regulation of several enzymes, we also explored the kinome. We hereby show that LMWPTP superactivation, together with kinome reprogramming, cooperate towards glucose addiction...
April 7, 2017: Journal of Cellular Biochemistry
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