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https://www.readbyqxmd.com/read/28542252/metabolic-flux-analysis-of-heterotrophic-growth-in-chlamydomonas-reinhardtii
#1
Nanette R Boyle, Neelanjan Sengupta, John A Morgan
Despite the wealth of knowledge available for C. reinhardtii, the central metabolic fluxes of growth on acetate have not yet been determined. In this study, 13C-metabolic flux analysis (13C-MFA) was used to determine and quantify the metabolic pathways of primary metabolism in C. reinhardtii cells grown under heterotrophic conditions with acetate as the sole carbon source. Isotopic labeling patterns of compartment specific biomass derived metabolites were used to calculate the fluxes. It was found that acetate is ligated with coenzyme A in the three subcellular compartments (cytosol, mitochondria and plastid) included in the model...
2017: PloS One
https://www.readbyqxmd.com/read/28542187/elucidation-of-new-condition-dependent-roles-for-fructose-1-6-bisphosphatase-linked-to-cofactor-balances
#2
Du Toit W P Schabort, Stephanus G Kilian, James C du Preez
The cofactor balances in metabolism is of paramount importance in the design of a metabolic engineering strategy and understanding the regulation of metabolism in general. ATP, NAD+ and NADP+ balances are central players linking the various fluxes in central metabolism as well as biomass formation. NADP+ is especially important in the metabolic engineering of yeasts for xylose fermentation, since NADPH is required by most yeasts in the initial step of xylose utilisation, including the fast-growing Kluyveromyces marxianus...
2017: PloS One
https://www.readbyqxmd.com/read/28534819/ginsenoside-rb2-alleviates-hepatic-lipid-accumulation-by-restoring-autophagy-via-induction-of-sirt1-and-activation-of-ampk
#3
Qi Huang, Ting Wang, Liu Yang, He-Yao Wang
Although Panax ginseng is a famous traditional Chinese medicine and has been widely used to treat a variety of metabolic diseases including hyperglycemia, hyperlipidemia, and hepatosteatosis, the effective mediators and molecular mechanisms remain largely unknown. In this study we found that ginsenoside Rb2, one of the major ginsenosides in Panax ginseng, was able to prevent hepatic lipid accumulation through autophagy induction both in vivo and in vitro. Treatment of male db/db mice with Rb2 significantly improved glucose tolerance, decreased hepatic lipid accumulation, and restored hepatic autophagy...
May 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28531184/bacarena-individual-based-metabolic-modeling-of-heterogeneous-microbes-in-complex-communities
#4
Eugen Bauer, Johannes Zimmermann, Federico Baldini, Ines Thiele, Christoph Kaleta
Recent advances focusing on the metabolic interactions within and between cellular populations have emphasized the importance of microbial communities for human health. Constraint-based modeling, with flux balance analysis in particular, has been established as a key approach for studying microbial metabolism, whereas individual-based modeling has been commonly used to study complex dynamics between interacting organisms. In this study, we combine both techniques into the R package BacArena (https://cran.r-project...
May 22, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28530276/focus-a-metaheuristic-algorithm-for-computing-knockouts-from-genome-scale-models-for-strain-optimization
#5
Sarma Mutturi
Although handful tools are available for constraint-based flux analysis to generate knockout strains, most of these are either based on bilevel-MIP or its modifications. However, metaheuristic approaches that are known for their flexibility and scalability have been less studied. Moreover, in the existing tools, sectioning of search space to find optimal knocks has not been considered. Herein, a novel computational procedure, termed as FOCuS (Flower-pOllination coupled Clonal Selection algorithm), was developed to find the optimal reaction knockouts from a metabolic network to maximize the production of specific metabolites...
May 22, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28522458/a-key-role-for-apoplastic-h2o2-in-norway-spruce-phenolic-metabolism
#6
Teresa Laitinen, Kris Morreel, Nicolas Delhomme, Adrien Gauthier, Bastian Schiffthaler, Kaloian Nickolov, Günter Brader, Kean-Jin Lim, Teemu H Teeri, Nathaniel R Street, Wout A Boerjan, Anna Karkonen
Apoplastic events such as monolignol oxidation and lignin polymerization are difficult to study in intact trees. To investigate the role of apoplastic H2O2 in gymnosperm phenolic metabolism, an extracellular lignin-forming cell culture of Norway spruce (Picea abies) was used as a research model. Scavenging of apoplastic H2O2 by KI repressed lignin formation, in line with peroxidases activating monolignols for lignin polymerization. Time course analyses coupled to candidate substrate product pair network propagation revealed differential accumulation of low-molecular-weight phenolics, including (glycosylated) oligolignols, (glycosylated) flavonoids and proanthocyanidins, in lignin-forming and H2O2-scavenging cultures, and supported that monolignols are oxidatively coupled not only in the cell wall, but also in the cytoplasm where they are coupled to other monolignols and proanthocyanidins...
May 18, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28520776/proteomic-analysis-of-tea-plants-camellia-sinensis-with-purple-young-shoots-during-leaf-development
#7
Qiongqiong Zhou, Zhidan Chen, Jinwook Lee, Xinghui Li, Weijiang Sun
Tea products made from purple leaves are highly preferred by consumers due to the health benefits. This study developed a proteome reference map related to color changes during leaf growth in tea (Camellia sinensis) plant with purple young shoots using two-dimensional electrophoresis (2-DE). Forty-six differentially expressed proteins were detected in the gel and successfully identified by using MALDI-TOF/TOF-MS. The pronounced changes in the proteomic profile between tender purple leaves (TPL) and mature green leaves (MGL) included: 1) the lower activity of proteins associated with CO2 assimilation, energy metabolism and photo flux efficiency and higher content of anthocyanins in TPL than those in MGL may protect tender leaves against photo-damage; 2) the higher abundance of chalcone synthase (CHS), chalcone isomerase (CHI) and flavonol synthase (FLS) likely contributes to the synthesis of anthocyanins, catechins and flavonols in TPL tissues; 3) higher abundance of stress response proteins, such as glutathione S-transferases (GST) and phospholipid hydroperoxide glutathione peroxidase (PHGPx), could enhance the tolerance of TPL tissues to adverse condition in; and 4) the increased abundance of proteins related to protein synthesis, nucleic acids and cell wall proteins should be beneficial for the proliferation and expansion of leaf cell in TPL tissues...
2017: PloS One
https://www.readbyqxmd.com/read/28515456/metabolomic-analysis-shows-differential-hepatic-effects-of-t2-and-t3-in-rats-after-short-term-feeding-with-high-fat-diet
#8
Liliana F Iannucci, Federica Cioffi, Rosalba Senese, Fernando Goglia, Antonia Lanni, Paul M Yen, Rohit A Sinha
Nonalcoholic fatty liver disease (NAFLD) is a major health problem worldwide, and is often associated with lipotoxic injury, defective mitochondrial function, and insulin resistance. Thyroid hormones (THs) are important regulators of hepatic lipid metabolism. Among the THs, diiodothyronine (T2) and triiodothyronine (T3) have shown promising results in lowering hepatic fat content in various models of NAFLD. In this study, we used a targeted metabolomics approach to investigate the differential effects of T2 and T3 on the early metabolic adaptation in the livers of rats fed high fat diet (HFD), a period when hepatosteatosis is reversible...
May 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28515149/pyruvate-kinase-inhibits-proliferation-during-postnatal-cerebellar-neurogenesis-and-suppresses-medulloblastoma-formation
#9
Katherine Tech, Andrey P Tikunov, Hamza Farooq, A Sorana Morrissy, Jessica Meidinger, Taylor Fish, Sarah C Green, Hedi Liu, Yisu Li, Andrew J Mungall, Richard A Moore, Yussanne Ma, Steven Jm Jones, Marco A Marra, Matthew G Vander Heiden, Michael D Taylor, Jeffrey MacDonald, Timothy R Gershon
Aerobic glycolysis supports proliferation through unresolved mechanisms. We have previously shown that aerobic glycolysis is required for the regulated proliferation of cerebellar granule neuron progenitors (CGNPs), and for the growth of CGNP-derived medulloblastoma. Blocking the initiation of glycolysis via deletion of Hexokinase-2 (Hk2) disrupts CGNP proliferation and restricts medulloblastoma growth. Here, we assessed whether disrupting Pyruvate kinase-M (Pkm), an enzyme that acts in the terminal steps of glycolysis, would alter CGNP metabolism, proliferation and tumorigenesis...
May 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28511646/emergence-of-microbial-diversity-due-to-cross-feeding-interactions-in-a-spatial-model-of-gut-microbial-metabolism
#10
Milan J A van Hoek, Roeland M H Merks
BACKGROUND: The human gut contains approximately 10(14) bacteria, belonging to hundreds of different species. Together, these microbial species form a complex food web that can break down nutrient sources that our own digestive enzymes cannot handle, including complex polysaccharides, producing short chain fatty acids and additional metabolites, e.g., vitamin K. Microbial diversity is important for colonic health: Changes in the composition of the microbiota have been associated with inflammatory bowel disease, diabetes, obesity and Crohn's disease, and make the microbiota more vulnerable to infestation by harmful species, e...
May 16, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28505258/modelling-and-mathematical-analysis-of-the-m-_-2-receptor-dependent-joint-signalling-and-secondary-messenger-network-in-cho-cells
#11
Benjamin Engelhardt, Janine Holze, Christina Elliott, George S Baillie, Maik Kschischo, Holger Fröhlich
The muscarinic M$_{2}$ receptor is a prominent member of the GPCR family and strongly involved in heart diseases. Recently published experimental work explored the cellular response to iperoxo-induced M$_{2}$ receptor stimulation in Chinese hamster ovary (CHO) cells. To better understand these responses, we modelled and analysed the muscarinic M$_{2}$ receptor-dependent signalling pathway combined with relevant secondary messenger molecules using mass action. In our literature-based joint signalling and secondary messenger model, all binding and phosphorylation events are explicitly taken into account in order to enable subsequent stoichiometric matrix analysis...
May 15, 2017: Mathematical Medicine and Biology: a Journal of the IMA
https://www.readbyqxmd.com/read/28505184/steadycom-predicting-microbial-abundances-while-ensuring-community-stability
#12
Siu Hung Joshua Chan, Margaret N Simons, Costas D Maranas
Genome-scale metabolic modeling has become widespread for analyzing microbial metabolism. Extending this established paradigm to more complex microbial communities is emerging as a promising way to unravel the interactions and biochemical repertoire of these omnipresent systems. While several modeling techniques have been developed for microbial communities, little emphasis has been placed on the need to impose a time-averaged constant growth rate across all members for a community to ensure co-existence and stability...
May 15, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28501379/metabolic-impact-of-nutrient-starvation-in-mevalonate-producing-escherichia-coli
#13
Ami Masuda, Yoshihiro Toya, Hiroshi Shimizu
The aim of this work was to enhance mevalonate yield from glucose in Escherichia coli by essential nutrient starvations and to reveal these effects on the central carbon metabolism. Stationary phase culture without essential nutrients such as nitrogen, sulfur, and magnesium was evaluated using an engineered E. coli introducing mvaE and mvaS genes from Enterococcus faecalis. Sulfur starvation resulted in the highest mevalonate yield of 0.61C-molC-mol(-1) from glucose. The metabolic impacts of nutrient starvation were investigated by (13)C-metabolic flux analysis...
May 4, 2017: Bioresource Technology
https://www.readbyqxmd.com/read/28499817/use-of-cellnetanalyzer-in-biotechnology-and-metabolic-engineering
#14
Axel von Kamp, Sven Thiele, Oliver Hädicke, Steffen Klamt
Mathematical models of the cellular metabolism have become an essential tool for the optimization of biotechnological processes. They help to obtain a systemic understanding of the metabolic processes in the used microorganisms and to find suitable genetic modifications maximizing the production performance. In particular, methods of stoichiometric and constraint-based modeling are frequently used in the context of metabolic and bioprocess engineering. Since metabolic networks can be complex and comprise hundreds or even thousands of metabolites and reactions, dedicated software tools are required for an efficient analysis...
May 9, 2017: Journal of Biotechnology
https://www.readbyqxmd.com/read/28480159/tracing-insights-into-human-metabolism-using-chemical-engineering-approaches
#15
Thekla Cordes, Christian M Metallo
Metabolism coordinates the conversion of available nutrients toward energy, biosynthetic intermediates, and signaling molecules to mediate virtually all biological functions. Dysregulation of metabolic pathways contributes to many diseases, so a detailed understanding of human metabolism has significant therapeutic implications. Over the last decade major technological advances in the areas of analytical chemistry, computational estimation of intracellular fluxes, and biological engineering have improved our ability to observe and engineer metabolic pathways...
November 2016: Current Opinion in Chemical Engineering
https://www.readbyqxmd.com/read/28479191/isotopically-nonstationary-13-c-flux-analysis-of-cyanobacterial-isobutyraldehyde-production
#16
Lara J Jazmin, Yao Xu, Yi Ern Cheah, Adeola O Adebiyi, Carl Hirschie Johnson, Jamey D Young
We applied isotopically nonstationary (13)C metabolic flux analysis (INST-MFA) to compare the pathway fluxes of wild-type (WT) Synechococcus elongatus PCC 7942 to an engineered strain (SA590) that produces isobutyraldehyde (IBA). The flux maps revealed a potential bottleneck at the pyruvate kinase (PK) reaction step that was associated with diversion of flux into a three-step PK bypass pathway involving the enzymes PEP carboxylase (PEPC), malate dehydrogenase (MDH), and malic enzyme (ME). Overexpression of pk in SA590 led to a significant improvement in IBA specific productivity...
May 4, 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/28476035/rewiring-carbohydrate-catabolism-differentially-affects-survival-of-pancreatic-cancer-cell-lines-with-diverse-metabolic-profiles
#17
Tiziana Tataranni, Francesca Agriesti, Vitalba Ruggieri, Carmela Mazzoccoli, Vittorio Simeon, Ilaria Laurenzana, Rosella Scrima, Valerio Pazienza, Nazzareno Capitanio, Claudia Piccoli
An increasing body of evidence suggests that targeting cellular metabolism represents a promising effective approach to treat pancreatic cancer, overcome chemoresistance and ameliorate patient's prognosis and survival. In this study, following whole-genome expression analysis, we selected two pancreatic cancer cell lines, PANC-1 and BXPC-3, hallmarked by distinct metabolic profiles with specific concern to carbohydrate metabolism. Functional comparative analysis showed that BXPC-3 displayed a marked deficit of the mitochondrial respiratory and oxidative phosphorylation activity and a higher production of reactive oxygen species and a reduced NAD+/NADH ratio, indicating their bioenergetic reliance on glycolysis and a different redox homeostasis as compared to PANC-1...
April 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28475656/nmr-based-metabolomic-analysis-for-the-effects-of-creatine-supplementation-on-mouse-myoblast-cell-line-c2c12
#18
Wenqi Xu, Donghai Lin, Caihua Huang
Creatine (Cr) supplementation has drawn much attention from researchers owing to its widespread efficacy in sports, and more recently, in therapeutic fields. However, the underlying molecular mechanisms remain elusive. Here, we performed nuclear magnetic resonance-based metabolomic analysis to address the metabolic profile of aqueous extracts from the mouse myoblast cell line C2C12 exposed to 2 mM Cr for 24 h (the Cr-treated group). Results showed that Cr supplementation facilitated the proliferation of C2C12 myoblasts...
May 5, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/28469419/an-insight-into-structure-function-and-expression-analysis-of-3-hydroxy-3-methylglutaryl-coa-reductase-of-cymbopogon-winterianus
#19
Kamalakshi Devi, Lochana Patar, Mahendra K Modi, Priyabrata Sen
Citronella (Cymbopogon winterianus) is one of the richest sources of high-value isoprenoid aromatic compounds used as flavour, fragrance, and therapeutic elements. These isoprenoid compounds are synthesized by 2 independent pathways: mevalonate pathway and 2-C-methyl-d-erythritol-4-phosphate pathway. Evidence suggests that 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) is a rate-controlling enzyme for the synthesis of variety of isoprenoids. This study reports the isolation, characterization, and tissue-specific expression analysis of HMGR from citronella...
2017: Bioinformatics and Biology Insights
https://www.readbyqxmd.com/read/28469410/modeling-fructose-load-induced-hepatic-de-novo-lipogenesis-by-model-simplification
#20
Richard J Allen, Cynthia J Musante
Hepatic de-novo lipogenesis is a metabolic process implemented in the pathogenesis of type 2 diabetes. Clinically, the rate of this process can be ascertained by use of labeled acetate and stimulation by fructose administration. A systems pharmacology model of this process is desirable because it facilitates the description, analysis, and prediction of this experiment. Due to the multiple enzymes involved in de-novo lipogenesis, and the limited data, it is desirable to use single functional expressions to encapsulate the flux between multiple enzymes...
2017: Gene Regulation and Systems Biology
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