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https://www.readbyqxmd.com/read/29785207/promiscuous-activities-of-heterologous-enzymes-lead-to-unintended-metabolic-rerouting-in-saccharomyces-cerevisiae-engineered-to-assimilate-various-sugars-from-renewable-biomass
#1
Eun Ju Yun, Eun Joong Oh, Jing-Jing Liu, Sora Yu, Dong Hyun Kim, Suryang Kwak, Kyoung Heon Kim, Yong-Su Jin
Background: Understanding the global metabolic network, significantly perturbed upon promiscuous activities of foreign enzymes and different carbon sources, is crucial for systematic optimization of metabolic engineering of yeast Saccharomyces cerevisiae . Here, we studied the effects of promiscuous activities of overexpressed enzymes encoded by foreign genes on rerouting of metabolic fluxes of an engineered yeast capable of assimilating sugars from renewable biomass by profiling intracellular and extracellular metabolites...
2018: Biotechnology for Biofuels
https://www.readbyqxmd.com/read/29784955/integration-of-large-scale-data-for-extraction-of-integrated-arabidopsis-root-cell-type-specific-models
#2
Michael Scheunemann, Siobhan M Brady, Zoran Nikoloski
Plant organs consist of multiple cell types that do not operate in isolation, but communicate with each other to maintain proper functions. Here, we extract models specific to three developmental stages of eight root cell types or tissue layers in Arabidopsis thaliana based on a state-of-the-art constraint-based modeling approach with all publicly available transcriptomics and metabolomics data from this system to date. We integrate these models into a multi-cell root model which we investigate with respect to network structure, distribution of fluxes, and concordance to transcriptomics and proteomics data...
May 21, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29777196/single-measurement-detection-of-individual-cell-ionic-oscillations-using-an-n-type-semiconductor-electrolyte-interface
#3
Mariusz Pietruszka, Monika Olszewska, Lukasz Machura, Edward Rówiński
Pollen tubes are used as models in studies on the type of tip-growth in plants. They are an example of polarised and rapid growth because pollen tubes are able to quickly invade the flower pistil in order to accomplish fertilisation. How different ionic fluxes are perceived, processed or generated in the pollen tube is still not satisfactorily understood. In order to measure the H+ , K+ , Ca2+ and Cl- fluxes of a single pollen tube, we developed an Electrical Lab on a Photovoltaic-Chip (ELoPvC) on which the evolving cell was immersed in an electrolyte of a germination medium...
May 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29775654/targeting-cancer-s-metabolic-co-dependencies-a-landscape-shaped-by-genotype-and-tissue-context
#4
REVIEW
Junfeng Bi, Sihan Wu, Wenjing Zhang, Paul S Mischel
Tumors cells reprogram their metabolism to fuel rapid growth. The ability to trace nutrient fluxes in the context of specific alterations has provided new mechanistic insight into the process of oncogenic transformation. A broad array of complementary genetic, epigenetic, transcriptional and translational mechanisms has been identified, revealing a metabolic landscape of cancer. However, cancer metabolism is not a static or uniform process, including within a single tumor. Tumor cells adapt to changing environmental conditions, profoundly shaping the enzymatic dependencies of individual cells...
May 15, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29774488/the-effect-of-oxygen-in-sirt3-mediated-myocardial-protection-a-proof-of-concept-study-in-cultured-cardiomyoblasts
#5
Philipp Diehl, Daniel S Gaul, Jonas Sogl, Ulrike Flierl, Darren Henstridge, Juergen Pahla, Heiko Bugger, Maximilian Y Emmert, Frank Ruschitzka, Christoph Bode, Thomas F Lüscher, Martin Moser, Christian M Matter, Karlheinz Peter, Stephan Winnik
Sirtuin 3 is a nicotinamide adenine dinucleotide dependent mitochondrial deacetylase that governs mitochondrial metabolism and oxidative defense. The demise in myocardial function following myocardial ischemia has been associated with mitochondrial dysfunction. Sirt3 maintains myocardial contractile function and protects from cardiac hypertrophy. The role of Sirt3 in ischemia is controversial. Our objective was to understand, under what circumstances Sirt3 is protective in different facets of ischemia, using an in vitro proof-of-concept approach based on simulated ischemia in cultured cardiomyoblasts...
May 17, 2018: Journal of Thrombosis and Thrombolysis
https://www.readbyqxmd.com/read/29774023/ferritin-h-deficiency-in-myeloid-compartments-dysregulates-host-energy-metabolism-and-increases-susceptibility-to-mycobacterium-tuberculosis-infection
#6
Vineel P Reddy, Krishna C Chinta, Vikram Saini, Joel N Glasgow, Travis D Hull, Amie Traylor, Fernanda Rey-Stolle, Miguel P Soares, Rajhmun Madansein, Md Aejazur Rahman, Coral Barbas, Kievershen Nargan, Threnesan Naidoo, Pratistadevi K Ramdial, James F George, Anupam Agarwal, Adrie J C Steyn
Iron is an essential factor for the growth and virulence of Mycobacterium tuberculosis ( Mtb) . However, little is known about the mechanisms by which the host controls iron availability during infection. Since ferritin heavy chain (FtH) is a major intracellular source of reserve iron in the host, we hypothesized that the lack of FtH would cause dysregulated iron homeostasis to exacerbate TB disease. Therefore, we used knockout mice lacking FtH in myeloid-derived cell populations to study Mtb disease progression...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29772843/the-role-of-trp-channels-in-the-metastatic-cascade
#7
REVIEW
Benedikt Fels, Etmar Bulk, Zoltán Pethő, Albrecht Schwab
A dysregulated cellular Ca2+ homeostasis is involved in multiple pathologies including cancer. Changes in Ca2+ signaling caused by altered fluxes through ion channels and transporters (the transportome) are involved in all steps of the metastatic cascade. Cancer cells thereby "re-program" and "misuse" the cellular transportome to regulate proliferation, apoptosis, metabolism, growth factor signaling, migration and invasion. Cancer cells use their transportome to cope with diverse environmental challenges during the metastatic cascade, like hypoxic, acidic and mechanical cues...
May 17, 2018: Pharmaceuticals
https://www.readbyqxmd.com/read/29769417/lactate-in-cardiogenic-shock-current-understanding-and-clinical-implications
#8
G M Kubiak, A R Tomasik, K Bartus, R Olszanecki, P Ceranowicz
Adenosine triphosphate (ATP) is an essential substrate metabolite in human beings. Mitochondrial oxidative phosphorylation provides > 95% of ATP with the remainder derived from glycolysis or tricarboxylic acid cycle (TCA). In normal hearts, acetyl-CoA is synthesized from the β-oxidation of free fatty acids (FFA) and the oxidation of pyruvate. Pyruvate is synthesized from glycolysis and can be submitted either for decarboxylation to acetyl-CoA or for dehydrogenation to lactate. Moreover, pyruvate, as well as lactate, plays a key role in aerobic glucose metabolism which is highly dependent on ubiquitous regulatory mechanisms...
February 2018: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/29769325/the-ancient-phosphatidylinositol-3-kinase-signaling-system-is-a-master-regulator-of-energy-and-carbon-metabolism-in-algae
#9
Rishiram Ramanan, Quynh-Giao Tran, Dae-Hyun Cho, Jae-Eun Jeong, Byung-Hyuk Kim, Sang-Yoon Shin, Sae-Hae Choi, Kwang-Hyeon Liu, Dae-Soo Kim, Seon-Jin Lee, Jose L Crespo, Hee-Gu Lee, Hee-Mock Oh, Hee-Sik Kim
Algae undergo a complete metabolic transformation under stress by arresting cell growth, inducing autophagy, and hyper-accumulating biofuel precursors such as triacylglycerols and starch. However, the regulatory mechanisms behind this stress-induced transformation are still unclear. Here, we use biochemical, mutational, and 'omics' approaches to demonstrate that phosphatidylinositol 3-kinase (PI3K) signaling mediates the homeostasis of energy molecules and influences carbon metabolism in algae. In Chlamydomonas reinhardtii, the inhibition and knockdown (KD) of algal class III PI3K led to significantly decreased cell growth, altered cell morphology, and higher lipid and starch contents...
May 16, 2018: Plant Physiology
https://www.readbyqxmd.com/read/29764852/combined-hdac-and-bromodomain-protein-inhibition-reprograms-tumor-cell-metabolism-and-elicits-synthetic-lethality-in-glioblastoma
#10
Yiru Zhang, Chiaki Tsuge Ishida, Wataru Ishida, Sheng-Fu L Lo, Junfei Zhao, Chang Shu, Elena Bianchetti, Giulio Kleiner, Maria Sanchez-Quintero, Catarina M Quinzii, Mike-Andrew Westhoff, Georg Karpel-Massler, Peter Canoll, Markus D Siegelin
PURPOSE: Glioblastoma remain a challenge in oncology in part due to tumor heterogeneity. EXPERIMENTAL DESIGN: Patient-derived xenograft and stem-like glioblastoma cells were used as the primary model systems. RESULTS: Based on a transcriptome and subsequent gene set enrichment analysis (GSEA), we show by using clinically validated compounds that combined histone deacetylase (HDAC) inhibition and Bromodomain protein (BRD) inhibition results in pronounced synergistic reduction in cellular viability in patient-derived xenograft and stem-like glioblastoma cells...
May 15, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29763898/fgfr4-links-glucose-metabolism-and-chemotherapy-resistance-in-breast-cancer
#11
Min Xu, Shuzheng Chen, Weibin Yang, Xue Cheng, Yani Ye, Jianting Mao, Xulu Wu, Li Huang, Jiansong Ji
BACKGROUND/AIMS: Poor response to chemotherapy leads to the relapse and metastatic progression of tumors. Reprogrammed glucose metabolism is one of the important hallmarks of cancer that facilitates cancer cell survival, proliferation and chemoresistance. However, the precise fate of glucose metabolism and its role in therapy responsiveness in cancers remains largely unexplored. METHODS: The glycolytic phenotype of doxorubicin (ADR)-resistant breast cancer cells and their parental cells was assessed by measuring glucose uptake, lactate release, and extracellular acidification rate (ECAR)...
May 10, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29763299/in-vivo-assimilation-of-one-carbon-via-a-synthetic-reductive-glycine-pathway-in-escherichia-coli
#12
Oren Yishai, Madeleine Bouzon, Volker Döring, Arren Bar-Even
Assimilation of one-carbon compounds presents a key biochemical challenge, which limits their use as sustainable feedstocks for microbial growth and production. The reductive glycine pathway is a synthetic metabolic route that could provide an optimal way for the aerobic assimilation of reduced C1 compounds. Here, we show that a rational integration of native and foreign enzymes enables the tetrahydrofolate and glycine cleavage/synthase systems to operate in the reductive direction, such that Escherichia coli satisfies all of its glycine and serine requirements from the assimilation of formate and CO2...
May 15, 2018: ACS Synthetic Biology
https://www.readbyqxmd.com/read/29761433/quantification-of-soluble-sugars-and-sugar-alcohols-by-lc-ms-ms
#13
Regina Feil, John Edward Lunn
Sugars are simple carbohydrates composed primarily of carbon, hydrogen, and oxygen. They play a central role in metabolism as sources of energy and as building blocks for synthesis of structural and nonstructural polymers. Many different techniques have been used to measure sugars, including refractometry, colorimetric and enzymatic assays, gas chromatography, high-performance liquid chromatography, and nuclear magnetic resonance spectroscopy. In this chapter we describe a method that combines an initial separation of sugars by high-performance anion-exchange chromatography (HPAEC) with detection and quantification by tandem mass spectrometry (MS/MS)...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29761431/carbon-atomic-survey-for-identification-of-selected-metabolic-fluxes
#14
Leonardo Perez de Souza, Alisdair R Fernie, Takayuki Tohge
Stable-isotope-labeling experiments have become a frequently used tool to investigate different metabolic systems. They have been recently applied to several comprehensive studies in plant metabolomics providing interesting insights into metabolic dynamics and regulation. However, the complexity of mass spectrometry data originating from such experiments is rarely fully explored. Data analysis often considers metabolites in their entirety which obscures important information at the atomic level. Recently, the use of mass spectrometry fragmentation for obtaining positional-labeling information was described for a few specific metabolites...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29761430/gas-chromatography-mass-spectrometry-based-13-c-labeling-studies-in-plant-metabolomics
#15
Valéria F Lima, Leonardo Perez de Souza, Thomas C R Williams, Alisdair R Fernie, Danilo M Daloso
Stable-isotope labeling analysis has been used to discover new metabolic pathways and their key regulatory points in a wide range of organisms. Given the complexity of the plant metabolic network, this analysis provides information complementary to that obtained from metabolite profiling that can be used to understand how plants cope with adverse conditions, and how metabolism varies between different cells, tissues, and organs. Here we describe the experimental procedures from sample harvesting and extraction to mass spectral analysis and interpretation that allow the researcher to perform 13 C-labeling experiments...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29760217/temporal-manipulation-of-mitochondrial-function-by-virulent-francisella-tularensis-to-limit-inflammation-and-control-cell-death
#16
Forrest Jessop, Benjamin Schwarz, Emily Heitmann, Robert Buntyn, Tara Wehrly, Catharine M Bosio
Francisella tularensis ssp tularensis (Ftt) is a highly pathogenic intracellular bacterium that suppresses host inflammation by impairing the metabolic shift from oxidative phosphorylation to glycolysis. Decreased mitochondrial metabolism is central to initiating a metabolic shift to glycolysis and regulating inflammation, but Ftt manipulation of host mitochondrial function has not been explored. We demonstrate using extracellular flux analysis that Ftt infection initially improves host macrophage mitochondrial bioenergetics in a capsule dependent manner...
May 14, 2018: Infection and Immunity
https://www.readbyqxmd.com/read/29755459/type-i-interferons-autophagy-and-host-metabolism-in-leprosy
#17
REVIEW
Thiago Gomes Toledo Pinto, Leonardo Ribeiro Batista-Silva, Rychelle Clayde Affonso Medeiros, Flávio Alves Lara, Milton Ozório Moraes
For those with leprosy, the extent of host infection by Mycobacterium leprae and the progression of the disease depend on the ability of mycobacteria to shape a safe environment for its replication during early interaction with host cells. Thus, variations in key genes such as those in pattern recognition receptors ( NOD2 and TLR1 ), autophagic flux ( PARK2, LRRK2 , and RIPK2 ), effector immune cytokines ( TNF and IL12 ), and environmental factors, such as nutrition, have been described as critical determinants for infection and disease progression...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29754225/sortase-a-assisted-metabolic-enzyme-ligation-in-escherichia-coli-for-enhancing-metabolic-flux
#18
Takuya Matsumoto, Tsutomu Tanaka, Akihiko Kondo
Metabolic engineering has been an important approach for microbial bio-production. To produce bio-chemicals with engineered microorganisms, metabolic pathways have been edited using several common strategies, including gene disruption, gene overexpression, and gene attenuation. Here, we demonstrated metabolic channeling based on enzymatic metabolic enzyme ligation as a noteworthy approach for enhancing a desired metabolic flux. To achieve metabolic channeling , the metabolic enzymes should be in close proximity in cells...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29753840/engineering-synergetic-co-2-fixing-pathways-for-malate-production
#19
Guipeng Hu, Jie Zhou, Xiulai Chen, Yuanyuan Qian, Cong Gao, Liang Guo, Peng Xu, Wei Chen, Jian Chen, Yin Li, Liming Liu
Increasing the microbial CO2 -fixing efficiency often requires supplying sufficient ATP and redirecting carbon flux for the production of metabolites. However, addressing these two issues concurrently remains a challenge. Here, we present a combinational strategy based on a synergetic CO2 -fixing pathway that combines an ATP-generating carboxylation reaction in the central metabolic pathway with the ATP-consuming RuBisCO shunt in the carbon fixation pathway. This strategy provides enough ATP to improve the efficiency of CO2 fixation and simultaneously rewires the CO2 -fixing pathway to the central metabolic pathway for the biosynthesis of chemicals...
May 10, 2018: Metabolic Engineering
https://www.readbyqxmd.com/read/29753645/reserve-flux-capacity-in-the-pentose-phosphate-pathway-enables-escherichia-coli-s-rapid-response-to-oxidative-stress
#20
Dimitris Christodoulou, Hannes Link, Tobias Fuhrer, Karl Kochanowski, Luca Gerosa, Uwe Sauer
To counteract oxidative stress and reactive oxygen species (ROS), bacteria evolved various mechanisms, primarily reducing ROS through antioxidant systems that utilize cofactor NADPH. Cells must stabilize NADPH levels by increasing flux through replenishing metabolic pathways like pentose phosphate (PP) pathway. Here, we investigate the mechanism enabling the rapid increase in NADPH supply by exposing Escherichia coli to hydrogen peroxide and quantifying the immediate metabolite dynamics. To systematically infer active regulatory interactions governing this response, we evaluated ensembles of kinetic models of glycolysis and PP pathway, each with different regulation mechanisms...
May 2, 2018: Cell Systems
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