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Pentose Phosphate Pathway

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https://www.readbyqxmd.com/read/29235513/metabolic-engineering-of-the-pentose-phosphate-pathway-for-enhanced-limonene-production-in-the-cyanobacterium-synechocysti-s-sp-pcc-6803
#1
Po-Cheng Lin, Rajib Saha, Fuzhong Zhang, Himadri B Pakrasi
Isoprenoids are diverse natural compounds, which have various applications as pharmaceuticals, fragrances, and solvents. The low yield of isoprenoids in plants makes them difficult for cost-effective production, and chemical synthesis of complex isoprenoids is impractical. Microbial production of isoprenoids has been considered as a promising approach to increase the yield. In this study, we engineered the model cyanobacterium Synechocystis sp. PCC 6803 for sustainable production of a commercially valuable isoprenoid, limonene...
December 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29231167/glucose-inhibits-cardiac-muscle-maturation-through-nucleotide-biosynthesis
#2
Haruko Nakano, Itsunari Minami, Daniel Braas, Herman Pappoe, Xiuju Wu, Addelynn Sagadevan, Laurent Vergnes, Kai Fu, Marco Morselli, Christopher Dunham, Xueqin Ding, Adam Z Stieg, James K Gimzewski, Matteo Pellegrini, Peter M Clark, Karen Reue, Aldons J Lusis, Bernard Ribalet, Siavash K Kurdistani, Heather Christofk, Norio Nakatsuji, Atsushi Nakano
The heart switches its energy substrate from glucose to fatty acids at birth, and maternal hyperglycemia is associated with congenital heart disease. However, little is known about how blood glucose impacts heart formation. Using a chemically defined human pluripotent stem-cell-derived cardiomyocyte differentiation system, we found that high glucose inhibits the maturation of cardiomyocytes at genetic, structural, metabolic, electrophysiological, and biomechanical levels by promoting nucleotide biosynthesis through the pentose phosphate pathway...
December 12, 2017: ELife
https://www.readbyqxmd.com/read/29230018/a-pck1-directed-glycogen-metabolic-program-regulates-formation-and-maintenance-of-memory-cd8-t-cells
#3
Ruihua Ma, Tiantian Ji, Huafeng Zhang, Wenqian Dong, Xinfeng Chen, Pingwei Xu, Degao Chen, Xiaoyu Liang, Xiaonan Yin, Yuying Liu, Jingwei Ma, Ke Tang, Yi Zhang, Yue'e Peng, Jinzhi Lu, Yi Zhang, Xiaofeng Qin, Xuetao Cao, Yonghong Wan, Bo Huang
CD8+ memory T (Tm) cells are fundamental for protective immunity against infections and cancers 1-5 . Metabolic activities are crucial in controlling memory T-cell homeostasis, but mechanisms linking metabolic signals to memory formation and survival remain elusive. Here we show that CD8+ Tm cells markedly upregulate cytosolic phosphoenolpyruvate carboxykinase (Pck1), the hub molecule regulating glycolysis, tricarboxylic acid cycle and gluconeogenesis, to increase glycogenesis via gluconeogenesis. The resultant glycogen is then channelled to glycogenolysis to generate glucose-6-phosphate and the subsequent pentose phosphate pathway (PPP) that generates abundant NADPH, ensuring high levels of reduced glutathione in Tm cells...
December 11, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/29216246/draft-genome-sequence-of-actinotignum-schaalii-dsm-15541t-genetic-insights-into-the-lifestyle-cell-fitness-and-virulence
#4
Atteyet F Yassin, Stefan Langenberg, Marcel Huntemann, Alicia Clum, Manoj Pillay, Krishnaveni Palaniappan, Neha Varghese, Natalia Mikhailova, Supratim Mukherjee, T B K Reddy, Chris Daum, Nicole Shapiro, Natalia Ivanova, Tanja Woyke, Nikos C Kyrpides
The permanent draft genome sequence of Actinotignum schaalii DSM 15541T is presented. The annotated genome includes 2,130,987 bp, with 1777 protein-coding and 58 rRNA-coding genes. Genome sequence analysis revealed absence of genes encoding for: components of the PTS systems, enzymes of the TCA cycle, glyoxylate shunt and gluconeogensis. Genomic data revealed that A. schaalii is able to oxidize carbohydrates via glycolysis, the nonoxidative pentose phosphate and the Entner-Doudoroff pathways. Besides, the genome harbors genes encoding for enzymes involved in the conversion of pyruvate to lactate, acetate and ethanol, which are found to be the end products of carbohydrate fermentation...
2017: PloS One
https://www.readbyqxmd.com/read/29216224/cytotoxicity-of-portoamides-in-human-cancer-cells-and-analysis-of-the-molecular-mechanisms-of-action
#5
Tiago Ribeiro, Filipa Lemos, Marco Preto, Joana Azevedo, Maria Lígia Sousa, Pedro N Leão, Alexandre Campos, Stig Linder, Rui Vitorino, Vitor Vasconcelos, Ralph Urbatzka
Portoamides are cyclic peptides produced and released by the cyanobacterial strain Phormidium sp. presumably to interfere with other organisms in their ecosystems ("allelopathy"). Portoamides were previously demonstrated to have an antiproliferative effect on human lung carcinoma cells, but the underlying mechanism of this activity has not been described. In the present work, the effects of portoamides on proliferation were examined in eight human cancer cell lines and two non-carcinogenic cell lines, and major differences in sensitivities were observed...
2017: PloS One
https://www.readbyqxmd.com/read/29212304/the-pentose-phosphate-pathway-as-a-potential-target-for-cancer-therapy
#6
REVIEW
Eunae Sandra Cho, Yong Hoon Cha, Hyun Sil Kim, Nam Hee Kim, Jong In Yook
During cancer progression, cancer cells are repeatedly exposed to metabolic stress conditions in a resource-limited environment which they must escape. Increasing evidence indicates the importance of nicotinamide adenine dinucleotide phosphate (NADPH) homeostasis in the survival of cancer cells under metabolic stress conditions, such as metabolic resource limitation and therapeutic intervention. NADPH is essential for scavenging of reactive oxygen species (ROS) mainly derived from oxidative phosphorylation required for ATP generation...
December 7, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/29210635/potential-drug-targets-in-the-pentose-phosphate-pathway-of-trypanosomatids
#7
Ines Loureiro, Joana Faria, Nuno Santarem, Terry K Smith, Joana Tavares, Anabela Cordeiro-da-Silva
The trypanosomatids, Trypanosoma brucei, Trypanosoma cruzi and Leishmania spp, are causative agents of important human diseases such African sleeping sickness, Chagas' disease and Leishmaniasis, respectively. The high impact of these diseases on human health and economy worldwide, the unsatisfactory available chemotherapeutic options and the absence of human effective vaccines, strongly justifies the search for new drugs. The pentose phosphate pathway has been proposed to be a viable strategy to defeat several infectious diseases, including those from trypanosomatids, as it includes an oxidative branch, important in the maintenance of cell redox homeostasis, and a non-oxidative branch in which ribose 5-phosphate and erythrose 4-phosphate, precursors of nucleic acids and aromatic amino acids, are produced...
December 5, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29203223/expression-of-heterologous-non-oxidative-pentose-phosphate-pathway-from-bacillus-methanolicus-and-phosphoglucose-isomerase-deletion-improves-methanol-assimilation-and-metabolite-production-by-a-synthetic-escherichia-coli-methylotroph
#8
R Kyle Bennett, Jacqueline E Gonzalez, W Brian Whitaker, Maciek R Antoniewicz, Eleftherios T Papoutsakis
Synthetic methylotrophy aims to develop non-native methylotrophic microorganisms to utilize methane or methanol to produce chemicals and biofuels. We report two complimentary strategies to further engineer a previously engineered methylotrophic E. coli strain for improved methanol utilization. First, we demonstrate improved methanol assimilation in the presence of small amounts of yeast extract by expressing the non-oxidative pentose phosphate pathway (PPP) from Bacillus methanolicus. Second, we demonstrate improved co-utilization of methanol and glucose by deleting the phosphoglucose isomerase gene (pgi), which rerouted glucose carbon flux through the oxidative PPP...
December 5, 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/29193384/concurrent-isotope-assisted-metabolic-flux-analysis-and-transcriptome-profiling-reveal-responses-of-poplar-cells-to-altered-nitrogen-and-carbon-supply
#9
Xiaofeng Zhang, Ashish Misra, Shilpa Nargund, Gary D Coleman, Ganesh Sriram
Reduced nitrogen is indispensable to plants. However, its limited availability in soil combined with the energetic and environmental impacts of nitrogen fertilizers motivates research into molecular mechanisms toward improving plant nitrogen use efficiency (NUE). We performed a systems-level investigation of this problem by employing multiple 'omics methodologies on cell suspensions of hybrid poplar (Populus tremula x Populus alba). Acclimation and growth of the cell suspensions in four nutrient regimes ranging from abundant to deficient supplies of carbon and nitrogen revealed that cell growth under low-nitrogen levels was associated with substantially higher NUE...
November 29, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/29192500/comparative-proteomics-of-contrasting-maize-genotypes-provides-insights-into-salt-stress-tolerance-mechanisms
#10
Meijie Luo, Yanxin Zhao, Yuandong Wang, Zi Shi, Panpan Zhang, Yunxia Zhang, Wei Song, Jiuran Zhao
Salt stress is a major abiotic factor limiting maize yield. To characterize the mechanism underlying maize salt tolerance, we compared the seedling root proteomes of salt-tolerant Jing724 and salt-sensitive D9H. The germination rate and growth parameter values (weight and length) were higher for Jing724 than for D9H under saline conditions. Using an iTRAQ-based method, we identified 513 differentially regulated proteins (DRPs), with 83 and 386 DRPs specific to Jing724 and D9H, respectively. In salt-stressed Jing724, the DRPs were primarily associated with the pentose phosphate pathway, glutathione metabolism, and nitrogen metabolism...
December 1, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/29191950/metabolic-re-patterning-in-copd-airway-smooth-muscle-cells
#11
Charalambos Michaeloudes, Chih-Hsi Kuo, Gulam Haji, Donna K Finch, Andrew J Halayko, Paul Kirkham, Kian Fan Chung, Ian M Adcock
Chronic obstructive pulmonary disease (COPD) airways are characterised by thickening of airway smooth muscle, partly due to airway smooth muscle cell (ASMC) hyperplasia. Metabolic reprogramming involving increased glycolysis and glutamine catabolism supports the biosynthetic and redox balance required for cellular growth. We examined whether COPD ASMCs show a distinct metabolic phenotype that may contribute to increased growth.We performed an exploratory intracellular metabolic profile analysis of ASMCs from healthy nonsmokers, healthy smokers and COPD patients, under unstimulated or growth conditions of transforming growth factor (TGF)-β and fetal bovine serum (FBS)...
November 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/29190376/p53-promotes-akt-and-sp1-dependent-metabolism-through-the-pentose-phosphate-pathway-that-inhibits-apoptosis-in-response-to-nutlin-3a
#12
Lei Duan, Ricardo E Perez, Ling Chen, Lothar A Blatter, Carl G Maki
Nutlin-3a is a MDM2 antagonist and preclinical drug that activates p53. Cells with MDM2 gene amplification are especially prone to Nutlin-3a-induced apoptosis, though the basis for this is unclear. Glucose metabolism can inhibit apoptosis in response to Nutlin-3a through mechanisms that are incompletely understood. Glucose metabolism through the pentose phosphate pathway (PPP) produces NADPH that can protect cells from potentially lethal reactive oxygen species (ROS). We compared apoptosis and glucose metabolism in cancer cells with and without MDM2 gene amplification treated with Nutlin-3a...
November 27, 2017: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/29187559/reprograming-of-glucose-metabolism-by-zerumbone-suppresses-hepatocarcinogenesis
#13
Nissar Wani, Bo Zhang, Kun-Yu Teng, Juan Barajas, Tasneem Motiwala, Peng Hu, Lianbo Yu, Rafael Brüschweiler, Kalpana Ghoshal, Samson T Jacob
Hepatocellular carcinoma (HCC) is the most prevalent and a highly aggressive liver malignancy with limited therapeutic options. Here, the therapeutic potential of zerumbone, a sesquiterpene derived from the ginger plant Zingiber zerumbet, against HCC was explored. Zerumbone inhibited proliferation and clonogenic survival of HCC cells in a dose-dependent manner by arresting cell at the G2/M phase, and inducing apoptosis. To elucidate the underlying molecular mechanism, a phosphokinase array was performed that showed significant inhibition of the PI3K/AKT/mTOR and STAT3 signaling pathways in zerumbone treated HCC cells...
November 29, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29186975/mammalian-sulfur-amino-acid-metabolism-a-nexus-between-redox-regulation-nutrition-epigenetics-and-detoxification
#14
María Angeles Pajares, Dolores Pérez-Sala
SIGNIFICANCE: Transsulfuration allows conversion of methionine into cysteine using homocysteine as an intermediate. This pathway produces S-adenosylmethionine, a key metabolite for cell function, and provides 50% of the cysteine needed for hepatic glutathione synthesis. The route requires the intake of essential nutrients (e.g. methionine, vitamins) and is regulated by their availability. Transsulfuration presents multiple interconnections with epigenetics, ATP and glutathione synthesis, polyol and pentose phosphate pathways and detoxification that rely mostly in the exchange of substrates or products...
November 30, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/29179741/dietary-energy-drives-the-dynamic-response-of-bovine-rumen-viral-communities
#15
Christopher L Anderson, Matthew B Sullivan, Samodha C Fernando
BACKGROUND: Rumen microbes play a greater role in host energy acquisition than that of gut-associated microbes in monogastric animals. Although genome-enabled advancements are providing access to the vast diversity of uncultivated microbes, our understanding of variables shaping rumen microbial communities is in its infancy. Viruses have been shown to impact microbial populations through a myriad of processes, including cell lysis and reprogramming of host metabolism. However, little is known about the processes shaping the distribution of rumen viruses or how viruses may modulate microbial-driven processes in the rumen...
November 28, 2017: Microbiome
https://www.readbyqxmd.com/read/29177008/deciphering-cyanobacterial-phenotypes-for-fast-photoautotrophic-growth-via-isotopically-nonstationary-metabolic-flux-analysis
#16
Mary H Abernathy, Jingjie Yu, Fangfang Ma, Michelle Liberton, Justin Ungerer, Whitney D Hollinshead, Saratram Gopalakrishnan, Lian He, Costas D Maranas, Himadri B Pakrasi, Doug K Allen, Yinjie J Tang
Background: Synechococcus elongatus UTEX 2973 is the fastest growing cyanobacterium characterized to date. Its genome was found to be 99.8% identical to S. elongatus 7942 yet it grows twice as fast. Current genome-to-phenome mapping is still poorly performed for non-model organisms. Even for species with identical genomes, cell phenotypes can be strikingly different. To understand Synechococcus 2973's fast-growth phenotype and its metabolic features advantageous to photo-biorefineries, 13C isotopically nonstationary metabolic flux analysis (INST-MFA), biomass compositional analysis, gene knockouts, and metabolite profiling were performed on both strains under various growth conditions...
2017: Biotechnology for Biofuels
https://www.readbyqxmd.com/read/29170974/comparative-proteomic-analysis-of-amnion-membrane-transplantation-and-cross-linking-treatments-in-an-experimental-alkali-injury-model
#17
Sevgi Subasi, Ozgul Altintas, Murat Kasap, Nil Guzel, Gurler Akpinar, Suleyman Karaman
PURPOSE: In this study, by using a two-dimensional (2D) electrophoresis-based experimental approach, we aimed at understanding the nature of alkali injuries and the underlying mechanisms. A secondary aim was to compare the effects of cross-linking (CXL) and amnion membrane transplantation (AMT) on corneal protein compositions at the end of the early repair phase after injured with alkali. METHOD: The right corneas of 24 rabbits were injured with a 1 N solution of NaOH...
November 23, 2017: International Ophthalmology
https://www.readbyqxmd.com/read/29169374/id1-promotes-hepatocellular-carcinoma-proliferation-and-confers-chemoresistance-to-oxaliplatin-by-activating-pentose-phosphate-pathway
#18
Xin Yin, Bei Tang, Jing-Huan Li, Yan Wang, Lan Zhang, Xiao-Ying Xie, Bo-Heng Zhang, Shuang-Jian Qiu, Wei-Zhong Wu, Zheng-Gang Ren
BACKGROUND: Drug resistance is one of the major concerns in the treatment of hepatocellular carcinoma (HCC). The aim of the present study was to determine whether aberrant high expression of the inhibitor of differentiation 1(ID1) confers oxaliplatin-resistance to HCC by activating the pentose phosphate pathway (PPP). METHODS: Aberrant high expression of ID1 was detected in two oxaliplatin-resistant cell lines MHCC97H-OXA(97H-OXA) and Hep3B-OXA(3B-OXA). The lentiviral shRNA or control shRNA was introduced into the two oxaliplatin-resistant cell lines...
November 23, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29158891/overexpression-of-hypoxia-inducible-factor-and-metabolic-pathways-possible-targets-of-cancer
#19
REVIEW
Davinder Singh, Rohit Arora, Pardeep Kaur, Balbir Singh, Rahul Mannan, Saroj Arora
Cancer, the main cause of human deaths in the modern world is a group of diseases. Anticancer drug discovery is a challenge for scientists because of involvement of multiple survival pathways of cancer cells. An extensive study on the regulation of each step of these pathways may help find a potential cancer target. Up-regulated HIF-1 expression and altered metabolic pathways are two classical characteristics of cancer. Oxygen-dependent (through pVHL, PHDs, calcium-mediated) and independent (through growth factor signaling pathway, mdm2 pathway, HSP90) regulation of HIF-1α leads to angiogenesis, metastasis, and cell survival...
2017: Cell & Bioscience
https://www.readbyqxmd.com/read/29158483/noninvasive-liquid-diet-delivery-of-stable-isotopes-into-mouse-models-for-deep-metabolic-network-tracing
#20
Ramon C Sun, Teresa W-M Fan, Pan Deng, Richard M Higashi, Andrew N Lane, Anh-Thu Le, Timothy L Scott, Qiushi Sun, Marc O Warmoes, Ye Yang
Delivering isotopic tracers for metabolic studies in rodents without overt stress is challenging. Current methods achieve low label enrichment in proteins and lipids. Here, we report noninvasive introduction of (13)C6-glucose via a stress-free, ad libitum liquid diet. Using NMR and ion chromatography-mass spectrometry, we quantify extensive (13)C enrichment in products of glycolysis, the Krebs cycle, the pentose phosphate pathway, nucleobases, UDP-sugars, glycogen, lipids, and proteins in mouse tissues during 12 to 48 h of (13)C6-glucose feeding...
November 21, 2017: Nature Communications
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