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metabolic flux analysis

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https://www.readbyqxmd.com/read/28335577/gc-ms-metabolomic-analysis-to-reveal-the-metabolites-and-biological-pathways-involved-in-the-developmental-stages-and-tissue-response-of-panax-ginseng
#1
Jia Liu, Yang Liu, Yu Wang, Ann Abozeid, Yuan-Gang Zu, Xiao-Ning Zhang, Zhong-Hua Tang
Ginsenosides, the major compounds present in ginseng, are known to have numerous physiological and pharmacological effects. The physiological processes, enzymes and genes involved in ginsenoside synthesis in P. ginseng have been well characterized. However, relatively little information is known about the dynamic metabolic changes that occur during ginsenoside accumulation in ginseng. To explore this topic, we isolated metabolites from different tissues at different growth stages, and identified and characterized them by using gas chromatography coupled with mass spectrometry (GC-MS)...
March 21, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28334697/constraint-based-stoichiometric-modelling-from-single-organisms-to-microbial-communities
#2
REVIEW
Willi Gottstein, Brett G Olivier, Frank J Bruggeman, Bas Teusink
Microbial communities are ubiquitously found in Nature and have direct implications for the environment, human health and biotechnology. The species composition and overall function of microbial communities are largely shaped by metabolic interactions such as competition for resources and cross-feeding. Although considerable scientific progress has been made towards mapping and modelling species-level metabolism, elucidating the metabolic exchanges between microorganisms and steering the community dynamics remain an enormous scientific challenge...
November 2016: Journal of the Royal Society, Interface
https://www.readbyqxmd.com/read/28334215/systematic-inference-of-functional-phosphorylation-events-in-yeast-metabolism
#3
Yu Chen, Yonghong Wang, Jens Nielsen
Motivation: Protein phosphorylation is a post-translational modification that affects proteins by changing their structure and conformation in a rapid and reversible way, and it is an important mechanism for metabolic regulation in cells. Phosphoproteomics enables high-throughput identification of phosphorylation events on metabolic enzymes, but identifying functional phosphorylation events still requires more detailed biochemical characterization. Therefore, development of computational methods for investigating unknown functions of a large number of phosphorylation events identified by phosphoproteomics has received increased attention...
March 2, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28333921/bioenergetics-based-modeling-of-plasmodium-falciparum-metabolism-reveals-its-essential-genes-nutritional-requirements-and-thermodynamic-bottlenecks
#4
Anush Chiappino-Pepe, Stepan Tymoshenko, Meriç Ataman, Dominique Soldati-Favre, Vassily Hatzimanikatis
Novel antimalarial therapies are urgently needed for the fight against drug-resistant parasites. The metabolism of malaria parasites in infected cells is an attractive source of drug targets but is rather complex. Computational methods can handle this complexity and allow integrative analyses of cell metabolism. In this study, we present a genome-scale metabolic model (iPfa) of the deadliest malaria parasite, Plasmodium falciparum, and its thermodynamics-based flux analysis (TFA). Using previous absolute concentration data of the intraerythrocytic parasite, we applied TFA to iPfa and predicted up to 63 essential genes and 26 essential pairs of genes...
March 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28325918/robust-analysis-of-fluxes-in-genome-scale-metabolic-pathways
#5
Michael MacGillivray, Amy Ko, Emily Gruber, Miranda Sawyer, Eivind Almaas, Allen Holder
Constraint-based optimization, such as flux balance analysis (FBA), has become a standard systems-biology computational method to study cellular metabolisms that are assumed to be in a steady state of optimal growth. The methods are based on optimization while assuming (i) equilibrium of a linear system of ordinary differential equations, and (ii) deterministic data. However, the steady-state assumption is biologically imperfect, and several key stoichiometric coefficients are experimentally inferred from situations of inherent variation...
March 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28323016/identifying-the-shared-metabolic-objectives-of-glycerol-bioconversion-in-klebsiella-pneumoniae-under-different-culture-conditions
#6
Gongxian Xu, Caixia Li
This paper addresses the problem of identifying the shared metabolic objectives of glycerol bioconversion in Klebsiella pneumoniae for production of 1,3-propanediol (1,3-PD) under different culture conditions. To achieve this goal, we propose a multi-level programming model. This model includes three optimization problems, where the constraint region of the first level problem is implicitly determined by the other two optimization problems. The optimized objectives of the first and second level problems are to minimize the set of fluxes that are of major importance to glycerol metabolism and the difference between the observed fluxes and those computed by the model, respectively...
March 17, 2017: Journal of Biotechnology
https://www.readbyqxmd.com/read/28319438/systemic-deregulation-of-autophagy-upon-loss-of-als-and-ftd-linked-c9orf72
#7
Yon Ji, Janet Ugolino, Nathan Ryan Brady, Anne Hamacher-Brady, Jiou Wang
A genetic mutation in the C9orf72 gene causes the most common forms of neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The C9orf72 protein, predicted to be a DENN-family protein, is reduced in ALS and FTD, but its functions remain poorly understood. Using a 3110043O21Rik/C9orf72 knockout mouse model, as well as cellular analysis, we have found that loss of C9orf72 causes alterations in the signaling states of central autophagy regulators. In particular, C9orf72 depletion leads to reduced activity of MTOR, a negative regulator of macroautophagy/autophagy, and concomitantly increased TFEB levels and nuclear translocation...
March 20, 2017: Autophagy
https://www.readbyqxmd.com/read/28318624/treatment-tolerance-and-patient-reported-outcomes-favor-online-hemodiafiltration-compared-to-high-flux-hemodialysis-in-the-elderly
#8
Marion Morena, Audrey Jaussent, Lotfi Chalabi, Hélène Leray-Moragues, Leila Chenine, Alain Debure, Damien Thibaudin, Lynda Azzouz, Laure Patrier, Francois Maurice, Philippe Nicoud, Claude Durand, Bruno Seigneuric, Anne-Marie Dupuy, Marie-Christine Picot, Jean-Paul Cristol, Bernard Canaud
Large cohort studies suggest that high convective volumes associated with online hemodiafiltration may reduce the risk of mortality/morbidity compared to optimal high-flux hemodialysis. By contrast, intradialytic tolerance is not well studied. The aim of the FRENCHIE (French Convective versus Hemodialysis in Elderly) study was to compare high-flux hemodialysis and online hemodiafiltration in terms of intradialytic tolerance. In this prospective, open-label randomized controlled trial, 381 elderly chronic hemodialysis patients (over age 65) were randomly assigned in a one-to-one ratio to either high-flux hemodialysis or online hemodiafiltration...
March 15, 2017: Kidney International
https://www.readbyqxmd.com/read/28315323/increased-serotonin-signaling-contributes-to-the-warburg-effect-in-pancreatic-tumor-cells-under-metabolic-stress-and-promotes-growth-of-pancreatic-tumors-in-mice
#9
Shu-Heng Jiang, Jun Li, Fang-Yuan Dong, Jian-Yu Yang, De-Jun Liu, Xiao-Mei Yang, Ya-Hui Wang, Min-Wei Yang, Xue-Liang Fu, Xiao-Xin Zhang, Qing Li, Xiu-Feng Pang, Yan-Miao Huo, Jiao Li, Jun-Feng Zhang, Ho-Young Lee, Su-Jae Lee, Wen-Xin Qin, Jian-Ren Gu, Yong-Wei Sun, Zhi-Gang Zhang
BACKGROUND & AIMS: The desmoplasia and poor vascularity cause severe metabolic stress in pancreatic ductal adenocarcinomas (PDACs). Serotonin (5-HT) is a neuromodulator with neurotransmitter and neuroendocrine functions that contributes to tumorigenesis. We investigated the role of 5-HT signaling in the growth of pancreatic tumors. METHODS: We measured the levels of proteins that regulate 5-HT synthesis, packaging, and degradation in pancreata from Kras(G12D/+); Trp53(R172H/+); Pdx1-Cre; (KPC) mice, which develop pancreatic tumors, as well as in PDAC cell lines and a tissue microarray containing 81 human PDAC samples...
March 14, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28314371/intrauterine-growth-restriction-programs-the-hypothalamus-of-adult-male-rats-integrated-analysis-of-proteomic-and-metabolomic-data
#10
Amanda Paula Pedroso, Adriana Pereira de Souza, Ana Paula Segantine Dornellas, Lila Missae Oyama, Cláudia Maria Oller Nascimento, Gianni Mara Silva Santos, José C Rosa, Ricardo Pimenta Bertolla, Jelena Klawitter, Uwe Christians, Alexandre Keiji Tashima, Eliane Beraldi Ribeiro
Programming of hypothalamic functions regulating energy homeostasis may play a role in intrauterine growth restriction (IUGR)-induced adulthood obesity. The present study investigated the effects of IUGR on the hypothalamus proteome and metabolome of adult rats submitted to 50% protein-energy restriction throughout pregnancy. Proteomic and metabolomic analyzes were performed by data independent acquisition mass spectrometry and multiple reaction monitoring, respectively. At age 4 months, the restricted rats showed elevated adiposity, increased leptin and signs of insulin resistance...
March 17, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28302590/stable-isotope-analysis-of-dynamic-lipidomics
#11
Joost Brandsma, Andrew P Bailey, Grielof Koster, Alex P Gould, Anthony D Postle
Metabolic pathway flux is a fundamental element of biological activity, which can be quantified using a variety of mass spectrometric techniques to monitor incorporation of stable isotope-labelled substrates into metabolic products. This article contrasts developments in electrospray ionisation mass spectrometry (ESI-MS) for the measurement of lipid metabolism with more established gas chromatography mass spectrometry and isotope ratio mass spectrometry methodologies. ESI-MS combined with diagnostic tandem MS/MS scans permits the sensitive and specific analysis of stable isotope-labelled substrates into intact lipid molecular species without the requirement for lipid hydrolysis and derivatisation...
March 13, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28295777/can-ldl-cholesterol-be-too-low-possible-risks-of-extremely-low-levels
#12
Anders G Olsson, Bo Angelin, Gerd Assmann, Christoph J Binder, Ingemar Björkhem, Angel Cedazo-Minguez, Jonathan Cohen, Arnold von Eckardstein, Eduardo Farinaro, Dirk Müller-Wieland, Klaus G Parhofer, Paolo Parini, Robert S Rosenson, Jakob Starup-Linde, Matti J Tikkanen, Laurent Yvan-Charvet
Following the continuous accumulation of evidence supporting the beneficial role of reducing low-density lipoprotein cholesterol (LDL-C) levels in the treatment and prevention of atherosclerotic cardiovascular disease and its complications, therapeutic possibilities now exist to lower LDL-C to very low levels, similar to or even lower than those seen in newborns and nonhuman species. In addition to the important task of evaluating potential side-effects of such treatments, the question arises whether extremely low LDL-C levels per se may provoke adverse effects in humans...
March 14, 2017: Journal of Internal Medicine
https://www.readbyqxmd.com/read/28295163/cyanobacterial-carbon-metabolism-fluxome-plasticity-and-oxygen-dependence
#13
Ni Wan, Drew M DeLorenzo, Lian He, Le You, Cheryl M Immethun, George Wang, Edward E K Baidoo, Whitney Hollinshead, Jay D Keasling, Tae Seok Moon, Yinjie J Tang
Synechocystis sp. strain PCC 6803 has been widely used as a photo-biorefinery chassis. Based on its genome annotation, this species contains a complete TCA cycle, an Embden-Meyerhof-Parnas pathway (EMPP), an oxidative pentose phosphate pathway (OPPP), and an Entner-Doudoroff pathway (EDP). To evaluate how Synechocystis 6803 catabolizes glucose under heterotrophic conditions, we performed (13) C metabolic flux analysis, metabolite pool size analysis, gene knockouts, and heterologous expressions. The results revealed a cyclic mode of flux through the OPPP...
March 14, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/28291718/cystathionine-beta-synthase-deficiency-alters-hepatic-phospholipid-and-choline-metabolism-post-translational-repression-of-phosphatidylethanolamine-n-methyltransferase-is-a-consequence-rather-than-a-cause-of-liver-injury-in-homocystinuria
#14
René L Jacobs, Hua Jiang, John P Kennelly, David J Orlicky, Robert H Allen, Sally P Stabler, Kenneth N Maclean
Classical homocystinuria (HCU) due to inactivating mutation of cystathionine β-synthase (CBS) is a poorly understood life-threatening inborn error of sulfur metabolism. A previously described cbs-/- mouse model exhibits a semi-lethal phenotype due to neonatal liver failure. The transgenic HO mouse model of HCU exhibits only mild liver injury and recapitulates multiple aspects of the disease as it occurs in humans. Disruption of the methionine cycle in HCU has the potential to impact multiple aspect of phospholipid (PL) metabolism by disruption of both the Kennedy pathway and phosphatidylethanolamine N-methyltransferase (PEMT) mediated synthesis of phosphatidylcholine (PC)...
March 2, 2017: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/28289721/platelets-from-pulmonary-hypertension-patients-show-increased-mitochondrial-reserve-capacity
#15
Quyen L Nguyen, Catherine Corey, Pamela White, Annie Watson, Mark T Gladwin, Marc A Simon, Sruti Shiva
Accumulating evidence suggests that altered cellular metabolism is systemic in pulmonary hypertension (PH) and central to disease pathogenesis. However, bioenergetic changes in PH patients and their association with disease severity remain unclear. Here, we hypothesize that alteration in bioenergetic function is present in platelets from PH patients and correlates with clinical parameters of PH. Platelets isolated from controls and PH patients (n = 28) were subjected to extracellular flux analysis to determine oxygen consumption and glycolytic rates...
March 9, 2017: JCI Insight
https://www.readbyqxmd.com/read/28289085/the-small-protein-sgrt-controls-transport-activity-of-the-glucose-specific-phosphotransferase-system
#16
Chelsea R Lloyd, Seongjin Park, Jingyi Fei, Carin K Vanderpool
The bacterial small RNA (sRNA) SgrS has been a fruitful model for discovery of novel RNA-based regulatory mechanisms and new facets of bacterial physiology and metabolism. SgrS is one of only a few characterized dual-function sRNAs. SgrS can control gene expression post-transcriptionally via sRNA-mRNA base pairing interactions. Its second function is coding for the small protein SgrT. Previous work demonstrated that both functions contribute to relief of growth inhibition caused by glucose-phosphate stress, a condition characterized by disrupted glycolytic flux and accumulation of sugar-phosphates...
March 13, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28289083/growth-tradeoffs-accompany-the-emergence-of-glycolytic-metabolism-in-shewanella-oneidensis-mr-1
#17
Lon M Chubiz, Christopher J Marx
Bacteria increase metabolic capacity via acquisition of genetic material or by mutation to genes already present in the genome. Here, we explore the mechanisms and tradeoffs involved when Shewanella oneidensis, a bacterium that typically consumes small organic and amino acids, rapidly evolves to expand its metabolic capacity to catabolize glucose after a short period of adaptation to a glucose-rich environment. Using whole-genome sequencing and genetic approaches, we discovered that deletions in a region including the transcriptional repressor (nagR) that regulates expression of genes associated with catabolism of N-acetylglucosamine is the common basis for evolved glucose metabolism across populations...
March 13, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28276759/cloning-and-functional-analysis-of-two-sterol-c24-methyltransferase-1-smt1-genes-from-paris-polyphylla
#18
Hong-Yu Guan, Ping Su, Yu-Jun Zhao, Xia-Nan Zhang, Zhu-Bo Dai, Juan Guo, Yu-Ru Tong, Yu-Jia Liu, Tian-Yuan Hu, Yan Yin, Lin-Hui Gao, Wei Gao, Lu-Qi Huang
The biosynthetic pathways of phytosterols and steroidal saponins are located in two adjacent branches which share cycloartenol as substrate. The rate-limiting enzyme S-adenosyl-L-methionine-sterol-C24-methyltransferase 1 (SMT1) facilitates the metabolic flux toward phytosterols. It catalyzes the methylation of the cycloartenol in the side chain of the C24-alkyl group, to generate 24(28)-methylene cycloartenol. In this study, we obtained two full-length sequences of SMT1 genes from Pari polyphylla, designated PpSMT1-1 and PpSMT1-2...
February 23, 2017: Journal of Asian Natural Products Research
https://www.readbyqxmd.com/read/28274202/identification-of-constraints-influencing-the-bacterial-genomes-evolution-in-the-pvc-super-phylum
#19
Sandrine Pinos, Pierre Pontarotti, Didier Raoult, Vicky Merhej
BACKGROUND: Horizontal transfer plays an important role in the evolution of bacterial genomes, yet it obeys several constraints, including the ecological opportunity to meet other organisms, the presence of transfer systems, and the fitness of the transferred genes. Bacteria from the Planctomyctetes, Verrumicrobia, Chlamydiae (PVC) super-phylum have a compartmentalized cell plan delimited by an intracytoplasmic membrane that might constitute an additional constraint with particular impact on bacterial evolution...
March 9, 2017: BMC Evolutionary Biology
https://www.readbyqxmd.com/read/28272795/inhibition-of-prostate-cancer-proliferation-by-deferiprone
#20
Rui V Simões, Suresh Veeraperumal, Inna S Serganova, Natalia Kruchevsky, Joseph Varshavsky, Ronald G Blasberg, Ellen Ackerstaff, Jason A Koutcher
Cancer growth and proliferation rely on intracellular iron availability. We studied the effects of Deferiprone (DFP), a chelator of intracellular iron, on three prostate cancer cell lines: murine, metastatic TRAMP-C2; murine, non-metastatic Myc-CaP; and human, non-metastatic 22rv1. The effects of DFP were evaluated at different cellular levels: cell culture proliferation and migration; metabolism of live cells (time-course multi-nuclear magnetic resonance spectroscopy cell perfusion studies, with 1-(13) C-glucose, and extracellular flux analysis); and expression (Western blot) and activity of mitochondrial aconitase, an iron-dependent enzyme...
March 8, 2017: NMR in Biomedicine
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