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metabolic flux analysis

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https://www.readbyqxmd.com/read/29349465/exploring-candidate-biomarkers-for-lung-and-prostate-cancers-using-gene-expression-and-flux-variability-analysis
#1
Yazdan Asgari, Pegah Khosravi, Zahra Zabihinpour, Mahnaz Habibi
Genome-scale metabolic models have provided valuable resources for exploring changes in metabolism under normal and cancer conditions. However, metabolism itself is strongly linked to gene expression, so integration of gene expression data into metabolic models might improve the detection of genes involved in the control of tumor progression. Herein, we considered gene expression data as extra constraints to enhance the predictive powers of metabolic models. We reconstructed genome-scale metabolic models for lung and prostate, under normal and cancer conditions to detect the major genes associated with critical subsystems during tumor development...
January 19, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://www.readbyqxmd.com/read/29347381/maximum-entropy-modeling-of-metabolic-networks-by-constraining-growth-rate-moments-predicts-coexistence-of-phenotypes
#2
Daniele De Martino
In this work maximum entropy distributions in the space of steady states of metabolic networks are considered upon constraining the first and second moments of the growth rate. Coexistence of fast and slow phenotypes, with bimodal flux distributions, emerges upon considering control on the average growth (optimization) and its fluctuations (heterogeneity). This is applied to the carbon catabolic core of Escherichia coli where it quantifies the metabolic activity of slow growing phenotypes and it provides a quantitative map with metabolic fluxes, opening the possibility to detect coexistence from flux data...
December 2017: Physical Review. E
https://www.readbyqxmd.com/read/29335637/expression-profiling-of-host-and-virus-during-a-coccolithophore-bloom-provides-insights-into-the-role-of-viral-infection-in-promoting-carbon-export
#3
Uri Sheyn, Shilo Rosenwasser, Yoav Lehahn, Noa Barak-Gavish, Ron Rotkopf, Kay D Bidle, Ilan Koren, Daniella Schatz, Assaf Vardi
The cosmopolitan coccolithophore Emiliania huxleyi is a unicellular eukaryotic alga that forms vast blooms in the oceans impacting large biogeochemical cycles. These blooms are often terminated due to infection by the large dsDNA virus, E. huxleyi virus (EhV). It was recently established that EhV-induced modulation of E. huxleyi metabolism is a key factor for optimal viral infection cycle. Despite the huge ecological importance of this host-virus interaction, the ability to assess its spatial and temporal dynamics and its possible impact on nutrient fluxes is limited by current approaches that focus on quantification of viral abundance and biodiversity...
January 15, 2018: ISME Journal
https://www.readbyqxmd.com/read/29333574/unique-metabolic-activation-of-adipose-tissue-macrophages-in-obesity-promotes-inflammatory-responses
#4
Lily Boutens, Guido J Hooiveld, Sourabh Dhingra, Robert A Cramer, Mihai G Netea, Rinke Stienstra
AIMS/HYPOTHESIS: Recent studies have identified intracellular metabolism as a fundamental determinant of macrophage function. In obesity, proinflammatory macrophages accumulate in adipose tissue and trigger chronic low-grade inflammation, that promotes the development of systemic insulin resistance, yet changes in their intracellular energy metabolism are currently unknown. We therefore set out to study metabolic signatures of adipose tissue macrophages (ATMs) in lean and obese conditions...
January 14, 2018: Diabetologia
https://www.readbyqxmd.com/read/29321350/neuro-fuzzy-model-of-homocysteine-metabolism
#5
Shaik Mohammad Naushad, Akella Radha Rama Devi, Sriraman Nivetha, Ganapathy Lakshmitha, Alex Balraj Stanley, Tajamul Hussain, Vijay Kumar Kutala
In view of well-documented association of hyperhomocysteinaemia with a wide spectrum of diseases and higher incidence of vitamin deficiencies in Indians, we proposed a mathematical model to forecast the role of demographic and genetic variables in influencing homocysteinemetabolism and investigated the influence of life style modulations in controlling homocysteine levels. Total plasma homocysteine levels were measured in fasting samples using reverse phase HPLC. Multiple linear regression (MLR) and neuro-fuzzy models were developed...
December 2017: Journal of Genetics
https://www.readbyqxmd.com/read/29318410/flux-analysis-of-inborn-errors-of-metabolism
#6
D-J Reijngoud
Patients with an inborn error of metabolism (IEM) are deficient of an enzyme involved in metabolism, and as a consequence metabolism reprograms itself to reach a new steady state. This new steady state underlies the clinical phenotype associated with the deficiency. Hence, we need to know the flux of metabolites through the different metabolic pathways in this new steady state of the reprogrammed metabolism. Stable isotope technology is best suited to study this. In this review the progress made in characterizing the altered metabolism will be presented...
January 9, 2018: Journal of Inherited Metabolic Disease
https://www.readbyqxmd.com/read/29317677/isolation-and-characterization-of-key-genes-that-promote-flavonoid-accumulation-in-purple-leaf-tea-camellia-sinensis-l
#7
Xiujuan He, Xuecheng Zhao, Liping Gao, Xingxing Shi, Xinlong Dai, Yajun Liu, Tao Xia, Yunsheng Wang
There were several high concentrations of flavonoid components in tea leaves that present health benefits. A novel purple-leaf tea variety, 'Mooma1', was obtained from the natural hybrid population of Longjing 43 variety. The buds and young leaves of 'Mooma1' were displayed in bright red. HPLC and LC-MS analysis showed that anthocyanins and O-Glycosylated flavonols were remarkably accumulated in the leaves of 'Mooma1', while the total amount of catechins in purple-leaf leaves was slightly decreased compared with the control...
January 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29316921/insights-into-metabolic-osmoadaptation-of-the-ectoines-producer-bacterium-chromohalobacter-salexigens-through-a-high-quality-genome-scale-metabolic-model
#8
Francine Piubeli, Manuel Salvador, Montserrat Argandoña, Joaquín J Nieto, Vicente Bernal, Jose M Pastor, Manuel Cánovas, Carmen Vargas
BACKGROUND: The halophilic bacterium Chromohalobacter salexigens is a natural producer of ectoines, compatible solutes with current and potential biotechnological applications. As production of ectoines is an osmoregulated process that draws away TCA intermediates, bacterial metabolism needs to be adapted to cope with salinity changes. To explore and use C. salexigens as cell factory for ectoine(s) production, a comprehensive knowledge at the systems level of its metabolism is essential...
January 9, 2018: Microbial Cell Factories
https://www.readbyqxmd.com/read/29316787/reprogramming-one-carbon-metabolic-pathways-to-decouple-l-serine-catabolism-from-cell-growth-in-corynebacterium-glutamicum
#9
Yun Zhang, Xiuling Shang, Shujuan Lai, Yu Zhang, Qitiao Hu, Xin Chai, Bo Wang, Shuwen Liu, Tingyi Wen
L-Serine, the principal one-carbon source for DNA biosynthesis, is difficult for microorganisms to accumulate due to the coupling of L-serine catabolism and microbial growth. Here, we reprogrammed the one-carbon unit metabolic pathways in Corynebacterium glutamicum to decouple L-serine catabolism from cell growth. In silico model-based simulation showed a negative influence on glyA-encoding serine hydroxymethyltransferase flux with L-serine productivity. Attenuation of glyA transcription resulted in increased L-serine accumulation, and a decrease in purine pools, poor growth and longer cell shapes...
January 9, 2018: ACS Synthetic Biology
https://www.readbyqxmd.com/read/29312565/dissect-new-mechanistic-insights-for-geniposide-efficacy-on-the-hepatoprotection-using-multiomics-approach
#10
Shi Qiu, Aihua Zhang, Tianlei Zhang, Hui Sun, Yu Guan, Guangli Yan, Xijun Wang
A multi-omics approach could yield in-depth mechanistic insights. Here, we performed an integrated analysis of miRNAome, proteome and metabolome, aimed to investigate the underlying mechanism of active product geniposide in ethanol-induced apoptosis. We found that integrative meta-analysis identified 28 miRNAs, 20 proteins and 7 metabolites significantly differentially expressed, respectively. Further analysis identified geniposide extensively regulated multiple metabolism pathways and the most important related pathway was citrate cycle (TCA cycle)...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29300340/constraining-genome-scale-models-to-represent-the-bow-tie-structure-of-metabolism-for-13c-metabolic-flux-analysis
#11
Tyler W H Backman, David Ando, Jahnavi Singh, Jay D Keasling, Héctor García Martín
Determination of internal metabolic fluxes is crucial for fundamental and applied biology because they map how carbon and electrons flow through metabolism to enable cell function. 13 C Metabolic Flux Analysis ( 13 C MFA) and Two-Scale 13 C Metabolic Flux Analysis (2S- 13 C MFA) are two techniques used to determine such fluxes. Both operate on the simplifying approximation that metabolic flux from peripheral metabolism into central "core" carbon metabolism is minimal, and can be omitted when modeling isotopic labeling in core metabolism...
January 4, 2018: Metabolites
https://www.readbyqxmd.com/read/29296771/red-blood-cells-in-hemorrhagic-shock-a-critical-role-for-glutaminolysis-in-fueling-alanine-transamination-in-rats
#12
Julie A Reisz, Anne L Slaughter, Rachel Culp-Hill, Ernest E Moore, Christopher C Silliman, Miguel Fragoso, Erik D Peltz, Kirk C Hansen, Anirban Banerjee, Angelo D'Alessandro
Red blood cells (RBCs) are the most abundant host cell in the human body and play a critical role in oxygen transport and systemic metabolic homeostasis. Hypoxic metabolic reprogramming of RBCs in response to high-altitude hypoxia or anaerobic storage in the blood bank has been extensively described. However, little is known about the RBC metabolism following hemorrhagic shock (HS), the most common preventable cause of death in trauma, the global leading cause of total life-years lost. Metabolomics analyses were performed through ultra-high pressure liquid chromatography-mass spectrometry on RBCs from Sprague-Dawley rats undergoing HS (mean arterial pressure [MAP], <30 mm Hg) in comparison with sham rats (MAP, >80 mm Hg)...
July 25, 2017: Blood Advances
https://www.readbyqxmd.com/read/29284039/from-in-vivo-to-in-vitro-major-metabolic-alterations-take-place-in-hepatocytes-during-and-following-isolation
#13
Shamir Cassim, Valérie-Ann Raymond, Pascal Lapierre, Marc Bilodeau
The liver plays a key role in maintaining physiological homeostasis and hepatocytes are largely responsible for this. The use of isolated primary hepatocytes has become an essential tool for the study of nutrient physiology, xenobiotic metabolism and several liver pathologies. Since hepatocytes are removed from their normal environment, the isolation procedure and in vitro culture of primary hepatocytes is partially known to induce undesired metabolic changes. We aimed to perform a thorough metabolic profiling of primary cells before, during and after isolation using state-of-the-art techniques...
2017: PloS One
https://www.readbyqxmd.com/read/29278749/thermodynamic-analysis-of-computed-pathways-integrated-into-the-metabolic-networks-of-e-coli-and-synechocystis-reveals-contrasting-expansion-potential
#14
Johannes Asplund-Samuelsson, Markus Janasch, Elton P Hudson
Introducing biosynthetic pathways into an organism is both reliant on and challenged by endogenous biochemistry. Here we compared the expansion potential of the metabolic network in the photoautotroph Synechocystis with that of the heterotroph E. coli using the novel workflow POPPY (Prospecting Optimal Pathways with PYthon). First, E. coli and Synechocystis metabolomic and fluxomic data were combined with metabolic models to identify thermodynamic constraints on metabolite concentrations (NET analysis). Then, thousands of automatically constructed pathways were placed within each network and subjected to a network-embedded variant of the max-min driving force analysis (NEM)...
December 23, 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/29278688/stage-specific-metabolic-features-of-differentiating-neurons-implications-for-toxicant-sensitivity
#15
Johannes Delp, Simon Gutbier, Martin Cerff, Christin Zasada, Sebastian Niedenführ, Liang Zhao, Lena Smirnova, Thomas Hartung, Hanna Borlinghaus, Falk Schreiber, Jörg Bergemann, Jochem Gätgens, Martin Beyss, Salah Azzouzi, Tanja Waldmann, Stefan Kempa, Katharina Nöh, Marcel Leist
Developmental neurotoxicity (DNT) may be induced when chemicals disturb a key neurodevelopmental process, and many tests focus on this type of toxicity. Alternatively, DNT may occur when chemicals are cytotoxic only during a specific neurodevelopmental stage. The toxicant sensitivity is affected by the expression of toxicant targets and by resilience factors. Although cellular metabolism plays an important role, little is known how it changes during human neurogenesis, and how potential alterations affect toxicant sensitivity of mature vs...
December 24, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29259592/characterization-of-the-sorbitol-utilization-cluster-of-the-probiotic-pediococcus-parvulus-2-6-genetic-functional-and-complementation-studies-in-heterologous-hosts
#16
Adrian Pérez-Ramos, Maria L Werning, Alicia Prieto, Pasquale Russo, Giuseppe Spano, Mari L Mohedano, Paloma López
Pediococcus parvulus 2.6 secretes a 2-substituted (1,3)-β-D-glucan with prebiotic and immunomodulatory properties. It is synthesized by the GTF glycosyltransferase using UDP-glucose as substrate. Analysis of the P. parvulus 2.6 draft genome revealed the existence of a sorbitol utilization cluster of six genes (gutFRMCBA), whose products should be involved in sorbitol utilization and could generate substrates for UDP-glucose synthesis. Southern blot hybridization analysis showed that the cluster is located in a plasmid...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29250098/reconstruction-of-oryza-sativa-indica-genome-scale-metabolic-model-and-its-responses-to-varying-rubisco-activity-light-intensity-and-enzymatic-cost-conditions
#17
Ankita Chatterjee, Benazir Huma, Rahul Shaw, Sudip Kundu
To combat decrease in rice productivity under different stresses, an understanding of rice metabolism is needed. Though there are different genome scale metabolic models (GSMs) of Oryza sativa japonica, no GSM with gene-protein-reaction association exist for Oryza sativa indica. Here, we report a GSM, OSI1136 of O.s. indica, which includes 3602 genes and 1136 metabolic reactions and transporters distributed across the cytosol, mitochondrion, peroxisome, and chloroplast compartments. Flux balance analysis of the model showed that for varying RuBisCO activity (Vc/Vo) (i) the activity of the chloroplastic malate valve increases to transport reducing equivalents out of the chloroplast under increased photorespiratory conditions and (ii) glyceraldehyde-3-phosphate dehydrogenase and phosphoglycerate kinase can act as source of cytosolic ATP under decreased photorespiration...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/29240609/effects-of-propofol-on-cellular-bioenergetics-in-human-skeletal-muscle-cells
#18
Adéla Krajčová, Nils Gunnar Løvsletten, Petr Waldauf, Vladimír Frič, Moustafa Elkalaf, Tomáš Urban, Michal Anděl, Jan Trnka, G Hege Thoresen, František Duška
OBJECTIVES: Propofol may adversely affect the function of mitochondria and the clinical features of propofol infusion syndrome suggest that this may be linked to propofol-related bioenergetic failure. We aimed to assess the effect of therapeutic propofol concentrations on energy metabolism in human skeletal muscle cells. DESIGN: In vitro study on human skeletal muscle cells. SETTINGS: University research laboratories. SUBJECTS: Patients undergoing hip surgery and healthy volunteers...
December 13, 2017: Critical Care Medicine
https://www.readbyqxmd.com/read/29238275/13c-assisted-metabolic-flux-analysis-to-investigate-heterotrophic-and-mixotrophic-metabolism-in-cupriavidus-necator-h16
#19
Swathi Alagesan, Nigel P Minton, Naglis Malys
Introduction: Cupriavidus necator H16 is a gram-negative bacterium, capable of lithoautotrophic growth by utilizing hydrogen as an energy source and fixing carbon dioxide (CO2) through Calvin-Benson-Bassham (CBB) cycle. The potential to utilize synthesis gas (Syngas) and the prospects of rerouting carbon from polyhydroxybutyrate synthesis to value-added compounds makes C. necator an excellent chassis for industrial application. Objectives: In the context of lack of sufficient quantitative information of the metabolic pathways and to advance in rational metabolic engineering for optimized product synthesis in C...
2018: Metabolomics: Official Journal of the Metabolomic Society
https://www.readbyqxmd.com/read/29237121/towards-synthetic-biology-strategies-for-adipic-acid-production-an-in-silico-tool-for-combined-thermodynamics-and-stoichiometric-analysis-of-metabolic-networks
#20
Nils Jonathan Helmuth Averesch, Verónica Salazar Martínez, Lars K Nielsen, Jens Olaf Krömer
Adipic acid, a nylon-6,6 precursor, has recently gained popularity in synthetic biology. Here, 16 different production routes to adipic acid were evaluated using a novel tool for network-embedded thermodynamic analysis of elementary flux modes. The tool distinguishes between thermodynamically feasible and infeasible modes under determined metabolite concentrations, allowing the thermodynamic feasibility of theoretical yields to be assessed. Further, patterns that always caused infeasible flux distributions were identified, which will aid the development of tailored strain design...
December 13, 2017: ACS Synthetic Biology
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