共查询到20条相似文献,搜索用时 462 毫秒
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Background
Constraint-based flux analysis of metabolic network model quantifies the reaction flux distribution to characterize the state of cellular metabolism. However, metabolites are key players in the metabolic network and the current reaction-centric approach may not account for the effect of metabolite perturbation on the cellular physiology due to the inherent limitation in model formulation. Thus, it would be practical to incorporate the metabolite states into the model for the analysis of the network. 相似文献3.
Background
Constraint-based models allow the calculation of the metabolic flux states that can be exhibited by cells, standing out as a powerful analytical tool, but they do not determine which of these are likely to be existing under given circumstances. Typical methods to perform these predictions are (a) flux balance analysis, which is based on the assumption that cell behaviour is optimal, and (b) metabolic flux analysis, which combines the model with experimental measurements. 相似文献4.
Bin Rui Tie Shen Hong Zhou Jianping Liu Jiusheng Chen Xiaosong Pan Haiyan Liu Jihui Wu Haoran Zheng Yunyu Shi 《BMC systems biology》2010,4(1):122
Background
The cellular responses of bacteria to superoxide stress can be used to model adaptation to severe environmental changes. Superoxide stress promotes the excessive production of reactive oxygen species (ROS) that have detrimental effects on cell metabolic and other physiological activities. To antagonize such effects, the cell needs to regulate a range of metabolic reactions in a coordinated way, so that coherent metabolic responses are generated by the cellular metabolic reaction network as a whole. In the present study, we have used a quantitative metabolic flux analysis approach, together with measurement of gene expression and activity of key enzymes, to investigate changes in central carbon metabolism that occur in Escherichia coli in response to paraquat-induced superoxide stress. The cellular regulatory mechanisms involved in the observed global flux changes are discussed. 相似文献5.
Background
During cytokinesis, the cell's equator contracts against the cell's global stiffness. Identifying the biochemical basis for these mechanical parameters is essential for understanding how cells divide. To achieve this goal, the distribution and flux of the cell division machinery must be quantified. Here we report the first quantitative analysis of the distribution and flux of myosin-II, an essential element of the contractile ring. 相似文献6.
Background
Quantitative knowledge of intracellular fluxes is important for a comprehensive characterization of metabolic networks and their functional operation. In contrast to direct assessment of metabolite concentrations, in vivo metabolite fluxes must be inferred indirectly from measurable quantities in 13C experiments. The required experience, the complicated network models, large and heterogeneous data sets, and the time-consuming set-up of highly controlled experimental conditions largely restricted metabolic flux analysis to few expert groups. A conceptual simplification of flux analysis is the analytical determination of metabolic flux ratios exclusively from MS data, which can then be used in a second step to estimate absolute in vivo fluxes. 相似文献7.
Background
Stimulus Response Experiments to unravel the regulatory properties of metabolic networks are becoming more and more popular. However, their ability to determine enzyme kinetic parameters has proven to be limited with the presently available data. In metabolic flux analysis, the use of 13C labeled substrates together with isotopomer modeling solved the problem of underdetermined networks and increased the accuracy of flux estimations significantly. 相似文献8.
Lake-Ee Quek Christoph Wittmann Lars K Nielsen Jens O Krömer 《Microbial cell factories》2009,8(1):25-15
Background
The quantitative analysis of metabolic fluxes, i.e., in vivo activities of intracellular enzymes and pathways, provides key information on biological systems in systems biology and metabolic engineering. It is based on a comprehensive approach combining (i) tracer cultivation on 13C substrates, (ii) 13C labelling analysis by mass spectrometry and (iii) mathematical modelling for experimental design, data processing, flux calculation and statistics. Whereas the cultivation and the analytical part is fairly advanced, a lack of appropriate modelling software solutions for all modelling aspects in flux studies is limiting the application of metabolic flux analysis. 相似文献9.
Background
Genome-scale flux models are useful tools to represent and analyze microbial metabolism. In this work we reconstructed the metabolic network of the lactic acid bacteria Lactococcus lactis and developed a genome-scale flux model able to simulate and analyze network capabilities and whole-cell function under aerobic and anaerobic continuous cultures. Flux balance analysis (FBA) and minimization of metabolic adjustment (MOMA) were used as modeling frameworks. 相似文献10.
Background
Metabolism and its regulation constitute a large fraction of the molecular activity within cells. The control of cellular metabolic state is mediated by numerous molecular mechanisms, which in effect position the metabolic network flux state at specific locations within a mathematically-definable steady-state flux space. Post-translational regulation constitutes a large class of these mechanisms, and decades of research indicate that achieving a network flux state through post-translational metabolic regulation is both a complex and complicated regulatory problem. No analysis method for the objective, top-down assessment of such regulation problems in large biochemical networks has been presented and demonstrated. 相似文献11.
Qing-Yi Lu Xuemei Zhang Jieping Yang Vay-Liang W. Go Wai-Nang Lee 《Metabolomics : Official journal of the Metabolomic Society》2017,13(4):39
Introduction
Loquat leaf extract (LLE) is a mixture rich in terpenoids, and has broad biological activities including the inhibition of cancer cell growth. The exact metabolic mechanism of this growth inhibiting effect is not known.Objectives
We investigated the cellular metabolic effect of LLE, and ursolic acid (UA) on pancreatic cancer cells using a 13C carbon tracing technology.Methods
MIA PaCa-2 cells were cultured in medium containing [1, 2 13C2]-glucose in the presence of either LLE (50 µg/ml), UA (50 µM), or metformin (1 mM). The mass isotopomer distribution of glucose, lactate, ribose, glutamate and palmitate in medium was determined. Based on the mass isotopomer distribution in metabolites we were able to determine individual 13C enrichment (∑M?×?n) and the minimum fraction of new synthesis?(1-M0) in each metabolite. Several flux ratios of energy metabolic pathways were calculated from the mass isotopomer ratios of these metabolites.Results
We found that tumor viability was suppressed by LLE and UA in a dose dependent manner, and the tumor-inhibiting effect was associated with the changes in oxidative/non-oxidative pentose (Ox/Non-ox) and pyruvate dehydrogenase/isocitrate dehydrogenase (PDH/ICDH) flux ratios resulting in decreased new syntheses of ribose and fatty acids.Conclusion
Metabolic homeostasis (balance of fluxes) in cancer cells is maintained through the regulation of metabolic fluxes by oncogenes and tumor-suppressor genes. Treatment of MIA PaCa-2 cells by LLE, UA and metformin likely altered key metabolic flux ratios affecting metabolic homeostasis required for energy and macromolecular production in tumor growth.12.
Yohei Shinfuku Natee Sorpitiporn Masahiro Sono Chikara Furusawa Takashi Hirasawa Hiroshi Shimizu 《Microbial cell factories》2009,8(1):43
Background
In silico genome-scale metabolic models enable the analysis of the characteristics of metabolic systems of organisms. In this study, we reconstructed a genome-scale metabolic model of Corynebacterium glutamicum on the basis of genome sequence annotation and physiological data. The metabolic characteristics were analyzed using flux balance analysis (FBA), and the results of FBA were validated using data from culture experiments performed at different oxygen uptake rates. 相似文献13.
Gema Alcarraz-Vizán Susana Sánchez-Tena Mary Pat Moyer Marta Cascante 《Biochimica et Biophysica Acta (BBA)/General Subjects》2014
Background
Cancer cells have extremely active metabolism, which supports high proliferation rates. Metabolic profiles of human colon cancer cells have been extensively studied, but comparison with non-tumour counterparts has been neglected.Methods
Here we compared the metabolic flux redistribution in human colon adenocarcinoma cells (HT29) and the human colon healthy cell line NCM460 in order to identify the main pathways involved in metabolic reprogramming. Moreover, we explore if induction of differentiation in HT29 by trichostatin A (TSA) reverts the metabolic reprogramming to that of NCM460. Cells were incubated with [1,2-13C2]-d-glucose as a tracer, and Mass Isotopomer Distribution Analysis was applied to characterize the changes in the metabolic flux distribution profile of the central carbon metabolism.Results
We demonstrate that glycolytic rate and pentose phosphate synthesis are 25% lower in NCM460 with respect to HT29 cells. In contrast, Krebs cycle activity in the former was twice that recorded in the latter. Moreover, we show that TSA-induced HT29 cell differentiation reverts the metabolic phenotype to that of healthy NCM460 cells whereas TSA does not affect the metabolism of NCM460 cells.Conclusions
We conclude that pentose phosphate pathway, glycolysis, and Krebs cycle are key players of colon adenocarcinoma cellular metabolic remodeling and that NCM460 is an appropriate model to evaluate the results of new therapeutic strategies aiming to selectively target metabolic reprogramming.General significance
Our findings suggest that strategies to counteract robust metabolic adaptation in cancer cells might open up new avenues to design multiple hit and targeted therapies. 相似文献14.
Background
In recent years, constrained optimization – usually referred to as flux balance analysis (FBA) – has become a widely applied method for the computation of stationary fluxes in large-scale metabolic networks. The striking advantage of FBA as compared to kinetic modeling is that it basically requires only knowledge of the stoichiometry of the network. On the other hand, results of FBA are to a large degree hypothetical because the method relies on plausible but hardly provable optimality principles that are thought to govern metabolic flux distributions. 相似文献15.
Roland?Schwarz Patrick?Musch Axel?von Kamp Bernd?Engels Heiner?Schirmer Stefan?Schuster Thomas?Dandekar
Background
A number of algorithms for steady state analysis of metabolic networks have been developed over the years. Of these, Elementary Mode Analysis (EMA) has proven especially useful. Despite its low user-friendliness, METATOOL as a reliable high-performance implementation of the algorithm has been the instrument of choice up to now. As reported here, the analysis of metabolic networks has been improved by an editor and analyzer of metabolic flux modes. Analysis routines for expression levels and the most central, well connected metabolites and their metabolic connections are of particular interest. 相似文献16.
Background
Many computer studies have employed either dynamic simulation or metabolic flux analysis (MFA) to predict the behaviour of biochemical pathways. Dynamic simulation determines the time evolution of pathway properties in response to environmental changes, whereas MFA provides only a snapshot of pathway properties within a particular set of environmental conditions. However, owing to the large amount of kinetic data required for dynamic simulation, MFA, which requires less information, has been used to manipulate large-scale pathways to determine metabolic outcomes. 相似文献17.
Analysis of optimal phenotypic space using elementary modes as applied to Corynebacterium glutamicum
Background
Quantification of the metabolic network of an organism offers insights into possible ways of developing mutant strain for better productivity of an extracellular metabolite. The first step in this quantification is the enumeration of stoichiometries of all reactions occurring in a metabolic network. The structural details of the network in combination with experimentally observed accumulation rates of external metabolites can yield flux distribution at steady state. One such methodology for quantification is the use of elementary modes, which are minimal set of enzymes connecting external metabolites. Here, we have used a linear objective function subject to elementary modes as constraint to determine the fluxes in the metabolic network of Corynebacterium glutamicum. The feasible phenotypic space was evaluated at various combinations of oxygen and ammonia uptake rates. 相似文献18.
Andreas Wagner 《BMC evolutionary biology》2009,9(1):231
Background
Metabolic networks show great evolutionary plasticity, because they can differ substantially even among closely related prokaryotes. Any one metabolic network can also effectively compensate for the blockage of individual reactions by rerouting metabolic flux through other pathways. These observations, together with the continual discovery of new microbial metabolic pathways and enzymes, raise the possibility that metabolic networks are only weakly constrained in changing their complement of enzymatic reactions. 相似文献19.
Swee Ling Lim Zhunan Jia Yonghai Lu Hui Zhang Cheng Teng Ng Boon Huat Bay Han Ming Shen Choon Nam Ong 《Metabolomics : Official journal of the Metabolomic Society》2018,14(9):118
Introduction
Histologically lung cancer is classified into four major types: adenocarcinoma (Ad), squamous cell carcinoma (SqCC), large cell carcinoma (LCC), and small cell lung cancer (SCLC). Presently, our understanding of cellular metabolism among them is still not clear.Objectives
The goal of this study was to assess the cellular metabolic profiles across these four types of lung cancer using an untargeted metabolomics approach.Methods
Six lung cancer cell lines, viz., Ad (A549 and HCC827), SqCC (NCl-H226 and NCl-H520), LCC (NCl-H460), and SCLC (NCl-H526), were analyzed using liquid chromatography quadrupole time-of-flight mass spectrometry, with normal human small airway epithelial cells (SAEC) as the control group. The principal component analysis (PCA) was performed to identify the metabolic signatures that had characteristic alterations in each histological type. Further, a metabolite set enrichment analysis was performed for pathway analysis.Results
Compared to the SAEC, 31, 27, 34, 34, 32, and 39 differential metabolites mainly in relation to nucleotides, amino acid, and fatty acid metabolism were identified in A549, HCC827, NCl-H226, NCl-H520, NCl-H460, and NCl-H526 cells, respectively. The metabolic signatures allowed the six cancerous cell lines to be clearly separated in a PCA score plot.Conclusion
The metabolic signatures are unique to each histological type, and appeared to be related to their cell-of-origin and mutation status. The changes are useful for assessing the metabolic characteristics of lung cancer, and offer potential for the establishment of novel diagnostic tools for different origin and oncogenic mutation of lung cancer.20.