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metabolic flux analysis

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https://www.readbyqxmd.com/read/28435456/physiological-effects-of-ac4mannaz-and-optimization-of-metabolic-labeling-for-cell-tracking
#1
Sang-Soo Han, Dong-Eun Lee, Hye-Eun Shim, Sangmin Lee, Taekhee Jung, Jung-Hwa Oh, Hyang-Ae Lee, Sung-Hwan Moon, Jongho Jeon, Seokjoo Yoon, Kwangmeyung Kim, Sun-Woong Kang
Metabolic labeling techniques are powerful tools for cell labeling, tracking and proteomic analysis. However, at present, the effects of the metabolic labeling agents on cell metabolism and physiology are not known. To address this question, in this study, we analyzed the effects of cells treated with Ac4ManNAz through microarray analysis and analyses of membrane channel activity, individual bio-physiological properties, and glycolytic flux. According to the results, treatment with 50 μM Ac4ManNAz led to the reduction of major cellular functions, including energy generation capacity, cellular infiltration ability and channel activity...
2017: Theranostics
https://www.readbyqxmd.com/read/28428793/transcriptomics-targeted-metabolomics-and-gene-expression-of-blackberry-leaves-and-fruits-indicate-flavonoid-metabolic-flux-from-leaf-to-red-fruit
#2
Enrique Gutierrez, Ana García-Villaraco, José A Lucas, Ana Gradillas, F Javier Gutierrez-Mañero, Beatriz Ramos-Solano
Blackberries (Rubus spp.) are among the high added value food products relevant for human health due to the increasing evidence of the beneficial effects of polyphenols, which are very abundant in these fruits. Interestingly, these compounds also play a role on plant physiology, being especially relevant their role in plant defense against biotic and abiotic stress. Hence, we hypothesize that since blackberry fruits have high amounts of flavonols and anthocyanins, leaves would also have high amounts of these compounds, and can be studied as a source of active molecules; furthermore, leaf synthesis would support their high contents in fruits...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28428141/temporal-impact-of-the-vascular-wilt-pathogen-verticillium-dahliae-on-tomato-root-proteome
#3
Katja Witzel, Anja Buhtz, Rita Grosch
The soil-borne fungus Verticillium dahliae is the causal agent of wilting disease and affects a wide range of plant species worldwide. Here, we report on the time-resolved analysis of the tomato root proteome in response to fungal colonization. Tomato (Solanum lycopersicum cv. Hildares) was inoculated with V. dahliae at the two-leaf stage and roots were harvested at 7, 14 and 21 days post inoculation (dpi). In order to identify proteins related to the fungal spread at the different time points, a subsequent proteome analysis by two-dimensional differential gel electrophoresis (2D-DIGE) was conducted on samples from three independent experiments...
April 17, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28424826/synergizing-13-c-metabolic-flux-analysis-and-metabolic-engineering-for-biochemical-production
#4
Weihua Guo, Jiayuan Sheng, Xueyang Feng
Metabolic engineering of industrial microorganisms to produce chemicals, fuels, and drugs has attracted increasing interest as it provides an environment-friendly and renewable route that does not depend on depleting petroleum sources. However, the microbial metabolism is so complex that metabolic engineering efforts often have difficulty in achieving a satisfactory yield, titer, or productivity of the target chemical. To overcome this challenge, (13)C Metabolic Flux Analysis ((13)C-MFA) has been developed to investigate rigorously the cell metabolism and quantify the carbon flux distribution in central metabolic pathways...
April 20, 2017: Advances in Biochemical Engineering/biotechnology
https://www.readbyqxmd.com/read/28420402/sser-species-specific-essential-reactions-database
#5
Abraham A Labena, Yuan-Nong Ye, Chuan Dong, Fa-Z Zhang, Feng-Biao Guo
BACKGROUND: Essential reactions are vital components of cellular networks. They are the foundations of synthetic biology and are potential candidate targets for antimetabolic drug design. Especially if a single reaction is catalyzed by multiple enzymes, then inhibiting the reaction would be a better option than targeting the enzymes or the corresponding enzyme-encoding gene. The existing databases such as BRENDA, BiGG, KEGG, Bio-models, Biosilico, and many others offer useful and comprehensive information on biochemical reactions...
April 19, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28419089/erroneous-energy-generating-cycles-in-published-genome-scale-metabolic-networks-identification-and-removal
#6
Claus Jonathan Fritzemeier, Daniel Hartleb, Balázs Szappanos, Balázs Papp, Martin J Lercher
Energy metabolism is central to cellular biology. Thus, genome-scale models of heterotrophic unicellular species must account appropriately for the utilization of external nutrients to synthesize energy metabolites such as ATP. However, metabolic models designed for flux-balance analysis (FBA) may contain thermodynamically impossible energy-generating cycles: without nutrient consumption, these models are still capable of charging energy metabolites (such as ADP→ATP or NADP+→NADPH). Here, we show that energy-generating cycles occur in over 85% of metabolic models without extensive manual curation, such as those contained in the ModelSEED and MetaNetX databases; in contrast, such cycles are rare in the manually curated models of the BiGG database...
April 18, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28418852/structural-homologies-between-phenformin-lipitor-and-gleevec-aim-the-same-metabolic-oncotarget-in-leukemia-and-melanoma
#7
REVIEW
Gábor Somlyai, T Que Collins, Emmanuelle J Meuillet, Patel Hitendra, Dominic P D'Agostino, László G Boros
Phenformin's recently demonstrated efficacy in melanoma and Gleevec's demonstrated anti-proliferative action in chronic myeloid leukemia may lie within these drugs' significant pharmacokinetics, pharmacodynamics and structural homologies, which are reviewed herein. Gleevec's success in turning a fatal leukemia into a manageable chronic disease has been trumpeted in medical, economic, political and social circles because it is considered the first successful targeted therapy. Investments have been immense in omics analyses and while in some cases they greatly helped the management of patients, in others targeted therapies failed to achieve clinically stable recurrence-free disease course or to substantially extend survival...
March 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28413815/data-documenting-the-comparison-between-the-theoretically-expected-values-of-free-sugars-mass-isotopomer-composition-with-standards-using-gc-ms-and-lc-hrms-for-metabolic-flux-analysis
#8
Sébastien Acket, Anthony Degournay, Franck Merlier, Brigitte Thomasset
The data presented in this article are related to the research article entitled "13C labeling analysis of sugars by high resolution-mass spectrometry for Metabolic Flux Analysis" (Acket et al., 2017) [1]. This article provides data concerning the comparison between the theoretically expected values of free sugars mass isotopomer composition with standards using our previous methods using low resolution mass spectrometry by GC-MS (Koubaa et al., 2012, 2014) [2,3], and your new method using high resolution-mass spectrometry (LC-HRMS) for Metabolic Flux Analysis [1]...
June 2017: Data in Brief
https://www.readbyqxmd.com/read/28412312/updates-to-a-13-c-metabolic-flux-analysis-model-for-evaluating-energy-metabolism-in-cultured-cerebellar-granule-neurons-from-neonatal-rats
#9
Mika B Jekabsons, Hoda M Gebril, Yan-Hong Wang, Bharathi Avula, Ikhlas A Khan
A hexose phosphate recycling model previously developed to infer fluxes through the major glucose consuming pathways in cultured cerebellar granule neurons (CGNs) from neonatal rats metabolizing [1,2-(13)C2]glucose was revised by considering reverse flux through the non-oxidative pentose phosphate pathway (PPP) and symmetrical succinate oxidation within the tricarboxylic acid (TCA) cycle. The model adjusts three flux ratios to effect (13)C distribution in the hexose, pentose, and triose phosphate pools, and in TCA cycle malate to minimize the error between predicted and measured (13)C labeling in exported lactate (i...
April 12, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28411229/a-comprehensive-analysis-of-myocardial-substrate-preference-emphasizes-the-need-for-a-synchronized-fluxomic-metabolomic-research-design
#10
Mukundan Ragavan, Alexander Kirpich, Xiaorong Fu, Shawn C Burgess, Lauren M McIntyre, Matthew E Merritt
The heart oxidizes fatty acids, carbohydrates and ketone bodies inside the citric acid cycle (CAC) to generate the reducing equivalents needed for ATP production. Competition between these substrates makes it difficult to estimate the extent of pyruvate oxidation. Previously, hyperpolarized pyruvate detected propionate mediated activation of carbohydrate oxidation, even in the presence of acetate. In this report, the optimal concentration of propionate for activation of glucose oxidation is measured in mouse hearts perfused in Langendorff mode...
April 14, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28410570/natural-selection-drove-metabolic-specialization-of-the-chromatophore-in-paulinella-chromatophora
#11
Cecilio Valadez-Cano, Roberto Olivares-Hernández, Osbaldo Resendis-Antonio, Alexander DeLuna, Luis Delaye
BACKGROUND: Genome degradation of host-restricted mutualistic endosymbionts has been attributed to inactivating mutations and genetic drift while genes coding for host-relevant functions are conserved by purifying selection. Unlike their free-living relatives, the metabolism of mutualistic endosymbionts and endosymbiont-originated organelles is specialized in the production of metabolites which are released to the host. This specialization suggests that natural selection crafted these metabolic adaptations...
April 14, 2017: BMC Evolutionary Biology
https://www.readbyqxmd.com/read/28406903/from-elementary-flux-modes-to-elementary-flux-vectors-metabolic-pathway-analysis-with-arbitrary-linear-flux-constraints
#12
REVIEW
Steffen Klamt, Georg Regensburger, Matthias P Gerstl, Christian Jungreuthmayer, Stefan Schuster, Radhakrishnan Mahadevan, Jürgen Zanghellini, Stefan Müller
Elementary flux modes (EFMs) emerged as a formal concept to describe metabolic pathways and have become an established tool for constraint-based modeling and metabolic network analysis. EFMs are characteristic (support-minimal) vectors of the flux cone that contains all feasible steady-state flux vectors of a given metabolic network. EFMs account for (homogeneous) linear constraints arising from reaction irreversibilities and the assumption of steady state; however, other (inhomogeneous) linear constraints, such as minimal and maximal reaction rates frequently used by other constraint-based techniques (such as flux balance analysis [FBA]), cannot be directly integrated...
April 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28404910/thalidezine-a-novel-ampk-activator-eliminates-apoptosis-resistant-cancer-cells-through-energy-mediated-autophagic-cell-death
#13
Betty Yuen Kwan Law, Flora Gordillo-Martínez, Yuan Qing Qu, Ni Zhang, Su Wei Xu, Paolo Saul Coghi, Simon Wing Fai Mok, Jianru Guo, Wei Zhang, Elaine Lai Han Leung, Xing Xing Fan, An Guo Wu, Wai Kit Chan, Xiao Jun Yao, Jing Rong Wang, Liang Liu, Vincent Kam Wai Wong
Cancers illustrating resistance towards apoptosis is one of the main factors causing clinical failure of conventional chemotherapy. Innovative therapeutic methods which can overcome the non-apoptotic phenotype are needed. The AMP-activated protein kinase (AMPK) is the central regulator of cellular energy homeostasis, metabolism, and autophagy. Our previous study showed that the identified natural AMPK activator is able to overcome apoptosis-resistant cancer via autophagic cell death. Therefore, AMPK is an ideal pharmaceutical target for chemoresistant cancers...
February 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28404660/the-genetic-requirements-for-pentose-fermentation-in-budding-yeast
#14
Karin Mittelman, Naama Barkai
Cells grow on a wide range of carbon sources by regulating substrate flow through the metabolic network. Incoming sugar, for example, can be fermented or respired, depending on the carbon identity, cell type, or growth conditions. Despite this genetically-encoded flexibility of carbon metabolism, attempts to exogenously manipulate central carbon flux by rational design have proven difficult, suggesting a robust network structure. To examine this robustness, we characterized the ethanol yield of 411 regulatory and metabolic mutants in budding yeast...
April 12, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28401266/dynamic-flux-balance-analysis-with-nonlinear-objective-function
#15
Xiao Zhao, Stephan Noack, Wolfgang Wiechert, Eric von Lieres
Dynamic flux balance analysis (DFBA) extends flux balance analysis and enables the combined simulation of both intracellular and extracellular environments of microbial cultivation processes. A DFBA model contains two coupled parts, a dynamic part at the upper level (extracellular environment) and an optimization part at the lower level (intracellular environment). Both parts are coupled through substrate uptake and product secretion rates. This work proposes a Karush-Kuhn-Tucker condition based solution approach for DFBA models, which have a nonlinear objective function in the lower-level part...
April 11, 2017: Journal of Mathematical Biology
https://www.readbyqxmd.com/read/28400330/metabolomics-driven-approach-to-solving-a-coa-imbalance-for-improved-1-butanol-production-in-escherichia-coli
#16
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/28400329/deletion-of-type-i-glutamine-synthetase-deregulates-nitrogen-metabolism-and-increases-ethanol-production-in-clostridium-thermocellum
#17
Thomas Rydzak, David Garcia, David M Stevenson, Margaret Sladek, Dawn M Klingeman, Evert K Holwerda, Daniel Amador-Noguez, Steven D Brown, Adam M Guss
Clostridium thermocellum rapidly deconstructs cellulose and ferments resulting hydrolysis products into ethanol and other products, and is thus a promising platform organism for the development of cellulosic biofuel production via consolidated bioprocessing. While recent metabolic engineering strategies have targeted eliminating canonical fermentation products (acetate, lactate, formate, and H2), C. thermocellum also secretes amino acids, which has limited ethanol yields in engineered strains to approximately 70% of the theoretical maximum...
April 8, 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/28396843/clostridioides-difficile-630%C3%AE-erm-in-silico-and-in-vivo-quantitative-growth-and-extensive-polysaccharide-secretion
#18
Henning Dannheim, Sabine E Will, Dietmar Schomburg, Meina Neumann-Schaal
Antibiotic-associated infections with Clostridioides difficile are a severe and often lethal risk for hospitalized patients, and can also affect populations without these classical risk factors. For a rational design of therapeutical concepts, a better knowledge of the metabolism of the pathogen is crucial. Metabolic modeling can provide a simulation of quantitative growth and usage of metabolic pathways, leading to a deeper understanding of the organism. Here, we present an elaborate genome-scale metabolic model of C...
April 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28395029/mitochondrial-and-morphologic-alterations-in-native-human-corneal-endothelial-cells-associated-with-diabetes-mellitus
#19
Benjamin T Aldrich, Ursula Schlötzer-Schrehardt, Jessica M Skeie, Kimberlee A Burckart, Gregory A Schmidt, Cynthia R Reed, M Bridget Zimmerman, Friedrich E Kruse, Mark A Greiner
Purpose: To characterize changes in the energy-producing metabolic activity and morphologic ultrastructure of corneal endothelial cells associated with diabetes mellitus. Methods: Transplant suitable corneoscleral tissue was obtained from donors aged 50 to 75 years. We assayed 3-mm punches of endothelium-Descemet membrane for mitochondrial respiration and glycolysis activity using extracellular flux analysis of oxygen and pH, respectively. Transmission electron microscopy was used to assess qualitative and quantitative ultrastructural changes in corneal endothelial cells and associated Descemet membrane...
April 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28389915/implementation-of-data-dependent-isotopologue-fragmentation-in-13-c-based-metabolic-flux-analysis
#20
Teresa Mairinger, Stephan Hann
A novel analytical approach based on liquid chromatography coupled to quadrupole time of flight mass spectrometry, employing data-dependent triggering for analysis of isotopologue and tandem mass isotopomer fractions of metabolites of the primary carbon metabolism was developed. The implemented QTOFMS method employs automated MS/MS triggering of higher abundant, biologically relevant isotopologues for generating positional information of the respective metabolite. Using this advanced isotopologue selective fragmentation approach enables the generation of significant tandem mass isotopomer data within a short cycle time without compromising sensitivity...
April 7, 2017: Analytical and Bioanalytical Chemistry
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