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TCA cycle

Andreas Maus, Godefridus J Peters
Glioblastoma multiforme (GBM), or grade IV astrocytoma, is the most common type of primary brain tumor. It has a devastating prognosis with a 2-year-overall survival rate of only 26 % after standard treatment, which includes surgery, radiation, and adjuvant chemotherapy with temozolomide. Also lower grade gliomas are difficult to treat, because they diffusely spread into the brain, where extensive removal of tissue is critical. Better understanding of the cancer's biology is a key for the development of more effective therapy approaches...
October 17, 2016: Amino Acids
Lars Grossmann, Daniela Beisser, Christina Bock, Antonis Chatzinotas, Manfred Jensen, Angelika Preisfeld, Roland Psenner, Sven Rahmann, Sabina Wodniok, Jens Boenigk
Inferring ecosystem functioning and ecosystem services through inspections of the species inventory is a major aspect of ecological field studies. Ecosystem functions are often stable despite considerable species turnover. Using metatranscriptome analyses, we analyse a thus-far unparalleled freshwater dataset which comprises 21 mainland European freshwater lakes from the Sierra Nevada (Spain) to the Carpathian Mountains (Romania) and from northern Germany to the Apennines (Italy) and covers an altitudinal range from 38 m above sea level (a...
October 16, 2016: Molecular Ecology
Bo Sun, Xubin Wang, Ruili Cao, Qi Zhang, Qiao Liu, Meifeng Xu, Ming Zhang, Xiangbo Du, Fangting Dong, Xianzhong Yan
ETHNOPHARMACOLOGICAL RELEVANCE: Fuzi, the processed lateral root of Aconitum carmichaelii Debeaux, is a traditional Chinese medicine used for its analgesic, antipyretic, anti-rheumatoid arthritis and anti-inflammation effects; however, it is also well known for its toxicity. Gancao, the root of Glycyrrhiza uralensis Fisch., is often used concurrently with Fuzi to alleviate its toxicity. However, the mechanism of detoxication is still not well clear. AIM OF THE STUDY: In this study, the effect of Gancao on the metabolic changes induced by Fuzi was investigated by NMR-based metabonomic approaches...
October 13, 2016: Journal of Ethnopharmacology
Brett A Morris, Brian Burkel, Suzanne M Ponik, Jing Fan, John S Condeelis, Julio A Aguire-Ghiso, James Castracane, John M Denu, Patricia J Keely
Increased breast density attributed to collagen I deposition is associated with a 4-6 fold increased risk of developing breast cancer. Here, we assessed cellular metabolic reprogramming of mammary carcinoma cells in response to increased collagen matrix density using an in vitro 3D model. Our initial observations demonstrated changes in functional metabolism in both normal mammary epithelial cells and mammary carcinoma cells in response to changes in matrix density. Further, mammary carcinoma cells grown in high density collagen matrices displayed decreased oxygen consumption and glucose metabolism via the tricarboxylic acid (TCA) cycle compared to cells cultured in low density matrices...
October 8, 2016: EBioMedicine
Baijun Dong, Yujing Gao, Xunlei Kang, Hongchang Gao, Jin Zhang, Hua Guo, Mingjian J You, Wei Xue, Jinke Cheng, Yiran Huang
Metabolic shift toward aerobic glycolysis is a fundamental element contributing to the development and progression of clear cell renal cell carcinoma (ccRCC). We and others previously observed enhanced glycolysis and diminished tricarboxylic acid (TCA) cycle activity in ccRCC tissue. Here, by integrated gene expression and metabolomic analyses of 36 matched pairs of tumor and adjacent normal tissues, we showed that expression of Sentrin/SUMO-specific protease 1 (SENP1) is positively associated with glycolysis levels in ccRCC...
October 12, 2016: Oncotarget
Jennifer Popko, Cornelia Herrfurth, Kirstin Feussner, Till Ischebeck, Tim Iven, Richard Haslam, Mary Hamilton, Olga Sayanova, Jonathan Napier, Inna Khozin-Goldberg, Ivo Feussner
Oleaginous microalgae are considered as a promising resource for the production of biofuels. Especially diatoms arouse interest as biofuel producers since they are most productive in carbon fixation and very flexible to environmental changes in the nature. Naturally, triacylglycerol (TAG) accumulation in algae only occurs under stress conditions like nitrogen-limitation. We focused on Phaeodactylum strain Pt4 (UTEX 646), because of its ability to grow in medium with low salinity and therefore being suited when saline water is less available or for wastewater cultivation strategies...
2016: PloS One
Guozhu Ye, Yajie Chen, Hong-Ou Wang, Ting Ye, Yi Lin, Qiansheng Huang, Yulang Chi, Sijun Dong
Tetrabromobisphenol A and tetrachlorobisphenol A are halogenated bisphenol A (H-BPA), and has raised concerns about their adverse effects on the development of fetuses and infants, however, the molecular mechanisms are unclear, and related metabolomics studies are limited. Accordingly, a metabolomics study based on gas chromatography-mass spectrometry was employed to elucidate the molecular developmental toxicology of H-BPA using the marine medaka (Oryzias melastigmas) embryo model. Here, we revealed decreased synthesis of nucleosides, amino acids and lipids, and disruptions in the TCA (tricarboxylic acid) cycle, glycolysis and lipid metabolism, thus inhibiting the developmental processes of embryos exposed to H-BPA...
October 13, 2016: Scientific Reports
Eric L Allen, Danielle B Ulanet, David Pirman, Christopher E Mahoney, John Coco, Yaguang Si, Ying Chen, Lingling Huang, Jinmin Ren, Sung Choe, Michelle F Clasquin, Erin Artin, Zi Peng Fan, Giovanni Cianchetta, Joshua Murtie, Marion Dorsch, Shengfang Jin, Gromoslaw A Smolen
Although aberrant metabolism in tumors has been well described, the identification of cancer subsets with particular metabolic vulnerabilities has remained challenging. Here, we conducted an siRNA screen focusing on enzymes involved in the tricarboxylic acid (TCA) cycle and uncovered a striking range of cancer cell dependencies on OGDH, the E1 subunit of the alpha-ketoglutarate dehydrogenase complex. Using an integrative metabolomics approach, we identified differential aspartate utilization, via the malate-aspartate shuttle, as a predictor of whether OGDH is required for proliferation in 3D culture assays and for the growth of xenograft tumors...
October 11, 2016: Cell Reports
Stefan Christen, Doriane Lorendeau, Roberta Schmieder, Dorien Broekaert, Kristine Metzger, Koen Veys, Ilaria Elia, Joerg Martin Buescher, Martin Franz Orth, Shawn Michael Davidson, Thomas Georg Philipp Grünewald, Katrien De Bock, Sarah-Maria Fendt
Cellular proliferation depends on refilling the tricarboxylic acid (TCA) cycle to support biomass production (anaplerosis). The two major anaplerotic pathways in cells are pyruvate conversion to oxaloacetate via pyruvate carboxylase (PC) and glutamine conversion to α-ketoglutarate. Cancers often show an organ-specific reliance on either pathway. However, it remains unknown whether they adapt their mode of anaplerosis when metastasizing to a distant organ. We measured PC-dependent anaplerosis in breast-cancer-derived lung metastases compared to their primary cancers using in vivo (13)C tracer analysis...
October 11, 2016: Cell Reports
Bradley Smith, Xenia L Schafer, Aslihan Ambeskovic, Cody M Spencer, Hartmut Land, Joshua Munger
Metabolic reprogramming is critical to oncogenesis, but the emergence and function of this profound reorganization remain poorly understood. Here we find that cooperating oncogenic mutations drive large-scale metabolic reprogramming, which is both intrinsic to cancer cells and obligatory for the transition to malignancy. This involves synergistic regulation of several genes encoding metabolic enzymes, including the lactate dehydrogenases LDHA and LDHB and mitochondrial glutamic pyruvate transaminase 2 (GPT2)...
October 11, 2016: Cell Reports
Emi Yamano, Masahiro Sugimoto, Akiyoshi Hirayama, Satoshi Kume, Masanori Yamato, Guanghua Jin, Seiki Tajima, Nobuhito Goda, Kazuhiro Iwai, Sanae Fukuda, Kouzi Yamaguti, Hirohiko Kuratsune, Tomoyoshi Soga, Yasuyoshi Watanabe, Yosky Kataoka
Chronic fatigue syndrome (CFS) is a persistent and unexplained pathological state characterized by exertional and severely debilitating fatigue, with/without infectious or neuropsychiatric symptoms, lasting at least 6 consecutive months. Its pathogenesis remains incompletely understood. Here, we performed comprehensive metabolomic analyses of 133 plasma samples obtained from CFS patients and healthy controls to establish an objective diagnosis of CFS. CFS patients exhibited significant differences in intermediate metabolite concentrations in the tricarboxylic acid (TCA) and urea cycles...
October 11, 2016: Scientific Reports
B C Medeiros, A T Fathi, C D DiNardo, D A Pollyea, S M Chan, R Swords
Alterations to genes involved in cellular metabolism and epigenetic regulation are implicated in the pathogenesis of myeloid malignancies. Recurring mutations in isocitrate dehydrogenase (IDH) genes are detected in approximately 20% of adult patients with acute myeloid leukemia (AML) and 5% of adults with myelodysplastic syndromes (MDS). IDH proteins are homodimeric enzymes involved in diverse cellular processes, including adaptation to hypoxia, histone demethylation, and DNA modification. The IDH2 protein is localized in the mitochondria and is a critical component of the tricarboxylic acid (TCA, also called the 'citric acid' or Krebs) cycle...
October 10, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Chongchong Chen, Ming Hong, Ju Chu, Mingzhi Huang, Liming Ouyang, Xiwei Tian, Yingping Zhuang
A high erythromycin producing mutant strain Saccharopolyspora erythraea HL3168 E3-ΔmutB was constructed by deleting mutB (SACE_5639) gene encoding the beta subunit of methylmalonyl-CoA mutase of an industrial strain of S. erythraea HL3168 E3. Industrial media and process control strategies were adopted in a 5 L bioreactor for characterizing the physiological parameters. The total erythromycin titer and erythromycin A concentration in mutant were 46.9 (12740.5 μg/mL) and 64.9 % (8094.4 μg/mL) higher than those in original strain, respectively, which were comparable to industrial erythromycin production...
October 5, 2016: Bioprocess and Biosystems Engineering
Eugenio Alcalde, Paul David Fraser
The filamentous fungus Phycomyces blakesleeanus provides a renewable biosource of industrial high value compounds such as carotenes, other isoprenoids (ubiquinone and sterols), organic acids and fatty acids. Several Phycomyces mutants involved in the formation of β-carotene are available. For example the carA mutants have a leaky mutation in the phytoene synthase and produce significantly lower amount of carotenes, while the carB and carR mutants produce phytoene and lycopene respectively, due to a null mutation in the genes encoding the phytoene dehydrogenase and lycopene cyclase respectively...
October 4, 2016: Microbiology
Sensen Shen, Rui Weng, Linnan Li, Xinyuan Xu, Yu Bai, Huwei Liu
Autophagy-related protein 7 (Atg7) is essential in the formation of the autophagophore and is indispensable for autophagy induction. Autophagy will exist in lower level or even be blocked in cells without Atg7. Even though the possible signaling pathways of Atg7 have been proposed, the metabolomic responses under acute starvation in cells with and without Atg7 have not been elucidated. This study therefore was designed and aimed to reveal the metabolomics of Atg7-dependent autophagy through metabolomic analysis of Atg7(-/-) mouse embryonic fibroblast cells (MEFs) and wild-type MEFs along with the starvation time...
October 5, 2016: Scientific Reports
Man-Young Jung, Jong-Geol Kim, Jaap S Sinninghe Damsté, W Irene C Rijpstra, Eugene L Madsen, So-Jeong Kim, Heeji Hong, Ok-Ja Si, Melina Kerou, Christa Schleper, Sung-Keun Rhee
A wide diversity of ammonia-oxidizing archaea (AOA) within the phylum Thaumarchaeota exists and plays a key role in the N cycle in a variety of habitats. In this study, we isolated and characterized an ammonia-oxidizing archaeon, strain MY3, from a coal tar-contaminated sediment. Phylogenetically, strain MY3 falls in clade 'Nitrosocosmicus' of the thaumarchaeotal group I.1b. The cells of strain MY3 are large "walnut-like" cocci, divide by binary fission along a central cingulum, and form aggregates. Strain MY3 is mesophilic and neutrophilic...
October 4, 2016: Environmental Microbiology Reports
Kelli M Sas, Pradeep Kayampilly, Jaeman Byun, Viji Nair, Lucy M Hinder, Junguk Hur, Hongyu Zhang, Chengmao Lin, Nathan R Qi, George Michailidis, Per-Henrik Groop, Robert G Nelson, Manjula Darshi, Kumar Sharma, Jeffrey R Schelling, John R Sedor, Rodica Pop-Busui, Joel M Weinberg, Scott A Soleimanpour, Steven F Abcouwer, Thomas W Gardner, Charles F Burant, Eva L Feldman, Matthias Kretzler, Frank C Brosius, Subramaniam Pennathur
Diabetes is associated with altered cellular metabolism, but how altered metabolism contributes to the development of diabetic complications is unknown. We used the BKS db/db diabetic mouse model to investigate changes in carbohydrate and lipid metabolism in kidney cortex, peripheral nerve, and retina. A systems approach using transcriptomics, metabolomics, and metabolic flux analysis identified tissue-specific differences, with increased glucose and fatty acid metabolism in the kidney, a moderate increase in the retina, and a decrease in the nerve...
September 22, 2016: JCI Insight
Heng-Heng Xu, Shu-Jun Liu, Shun-Hua Song, Wei-Qing Wang, Ian Max Møller, Song-Quan Song
Seed dormancy provides optimum timing for seed germination and subsequent seedling growth, but the mechanism of seed dormancy is still poorly understood. Here, we used Dongxiang wild rice (DXWR) seeds to investigate the dormancy behavior and the differentially changed proteome in embryo and endosperm during dormancy release. DXWR seed dormancy was caused by interaction of embryo and its surrounding structure, and was an intermediate physiological dormancy. During seed dormancy release, a total of 109 and 97 protein spots showed significant change in abundance and were successfully identified in embryo and endosperm, respectively...
September 22, 2016: Journal of Plant Physiology
Wenhui Yang, Yan He, Shijie Liu, Lulu Gan, Zhiguo Zhang, Jun Wang, Jie Liang, Yang Dong, Qing Wang, Zongliu Hou, Li Yang
Dysregulation of metabolism in hepatocytes leads to hepatic diseases such as hepatitis and non-alcoholic fatty liver disease (NAFLD). NAFLD represents a spectrum of liver diseases ranging from simple steatosis to nonalcoholic steatohepatitis (NASH). NASH is likely to progress to cirrhosis, liver failure and hepatocellular carcinoma, which lead to poor long-term prognosis. However, the exact mechanism of development of NAFLD is not well elucidated. In order to better understand the pathogenesis of NAFLD, we have performed an integrative analysis to livers from NAFLD rat models in a global view of the transcriptome...
September 30, 2016: Gene
Wenqin Bai, Yi-Shu Tai, Jingyu Wang, Jilong Wang, Pooja Jambunathan, Kevin J Fox, Kechun Zhang
Dicarboxylic acids are attractive biosynthetic targets due to their broad applications and their challenging manufacturing process from fossil fuel feedstock. Mesaconate is a branched, unsaturated dicarboxylic acid that can be used as a co-monomer to produce hydrogels and fire-retardant materials. In this study, we engineered nonphosphorylative metabolism to produce mesaconate from d-xylose and l-arabinose. This nonphosphorylative metabolism is orthogonal to the intrinsic pentose metabolism in Escherichia coli and has fewer enzymatic steps and a higher theoretical yield to TCA cycle intermediates than the pentose phosphate pathway...
September 30, 2016: Metabolic Engineering
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