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Pyruvate carboxylase

Teresa Delgado-Goni, Maria Falck Miniotis, Slawomir Wantuch, Harold G Parkes, Richard Marais, Paul Workman, Martin O Leach, Mounia Beloueche-Babari
Understanding the impact of BRAF signaling inhibition in human melanoma on key disease mechanisms is important for developing biomarkers of therapeutic response and combination strategies to improve long term disease control. This work investigates the downstream metabolic consequences of BRAF inhibition with vemurafenib, the molecular and biochemical processes that underpin them, their significance for antineoplastic activity and potential as non-invasive imaging response biomarkers.(1)H NMR spectroscopy showed that vemurafenib decreases the glycolytic activity of BRAF mutant (WM266...
October 7, 2016: Molecular Cancer Therapeutics
Peng-Fei Xia, Guo-Chang Zhang, Berkley Walker, Seung-Oh Seo, Suryang Kwak, Jingjing Liu, Heejin Kim, Donald Ort, Shu-Guang Wang, Yong-Su Jin
Global climate change caused by the emission of anthropogenic greenhouse gasses (GHGs) is a grand challenge to humanity. To alleviate the trend, the consumption of fossil fuels needs to be largely reduced and alternative energy technologies capable of controlling GHG emissions are anticipated. In this study, we introduced a synthetic reductive pentose phosphate pathway (rPPP) into a xylose-fermenting Saccharomyces cerevisiae strain SR8 to achieve simultaneous lignocellulosic bioethanol production and carbon dioxide recycling...
October 17, 2016: ACS Synthetic Biology
Md Abu Sayed, Yui Umekawa, Kikukatsu Ito
Skunk cabbage (Symplocarpus renifolius) blooms in early spring and its inflorescence, referred to as the spadix, can produce enough heat to melt snow. Here, we investigated glycolytic carbon flow at the PEP branch-point in thermogenic spadices. Our analyses revealed that petals and pistils in thermogenic florets exhibited higher expression of SrPEPC and SrAOX transcripts than those of SrPK, SrPEPCK, and SrPEPtase. Moreover, enzymatic analyses showed high activities of PEPC in the extracts from thermogenic florets...
October 14, 2016: Plant Signaling & Behavior
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
Laëtitia Riva-Roveda, Brigitte Escale, Catherine Giauffret, Claire Périlleux
BACKGROUND: European Flint maize inbred lines are used as a source of adaptation to cold in most breeding programs in Northern Europe. A deep understanding of their adaptation strategy could thus provide valuable clues for further improvement, which is required in the current context of climate change. We therefore compared six inbreds and two derived Flint x Dent hybrids for their response to one-week at low temperature (10 °C day/7 or 4 °C night) during steady-state vegetative growth...
October 4, 2016: BMC Plant Biology
Philip H Choi, Jeanyoung Jo, Yu-Cheng Lin, Min-Han Lin, Chi-Yuan Chou, Lars E P Dietrich, Liang Tong
Pyruvate carboxylase (PC) has important roles in metabolism and is crucial for virulence for some pathogenic bacteria. PC contains biotin carboxylase (BC), carboxyltransferase (CT) and biotin carboxyl carrier protein (BCCP) components. It is a single-chain enzyme in eukaryotes and most bacteria, and functions as a 500 kD homo-tetramer. In contrast, PC is a two-subunit enzyme in a collection of Gram-negative bacteria, with the α subunit containing the BC and the β subunit the CT and BCCP domains, and it is believed that the holoenzyme has α4β4 stoichiometry...
October 6, 2016: Nature Communications
Shuyan Zhang, Masakazu Ito, Jeffrey M Skerker, Adam P Arkin, Christopher V Rao
Natural lipids can be used to make biodiesel and many other value-added compounds. In this work, we explored a number of different metabolic engineering strategies for increasing lipid production in the oleaginous yeast Rhodosporidium toruloides IFO0880. These included increasing the expression of enzymes involved in different aspects of lipid biosynthesis-malic enzyme (ME), pyruvate carboxylase (PYC1), glycerol-3-P dehydrogenase (GPD), and stearoyl-CoA desaturase (SCD)-and deleting the gene PEX10, required for peroxisome biogenesis...
November 2016: Applied Microbiology and Biotechnology
Sowmyalakshmi Subramanian, Alfred Souleimanov, Donald L Smith
Plants, being sessile organisms, are exposed to widely varying environmental conditions throughout their life cycle. Compatible plant-microbe interactions favor plant growth and development, and help plants deal with these environmental challenges. Microorganisms produce a diverse range of elicitor molecules to establish symbiotic relationships with the plants they associate with, in a given ecological niche. Lipo-chitooligosaccharide (LCO) and Thuricin 17 (Th17) are two such compounds shown to positively influence plant growth of both legumes and non-legumes...
2016: Frontiers in Plant Science
Daniel Simão, Ana P Terrasso, Ana P Teixeira, Catarina Brito, Ursula Sonnewald, Paula M Alves
The generation of human neural tissue-like 3D structures holds great promise for disease modeling, drug discovery and regenerative medicine strategies. Promoting the establishment of complex cell-cell interactions, 3D culture systems enable the development of human cell-based models with increased physiological relevance, over monolayer cultures. Here, we demonstrate the establishment of neuronal and astrocytic metabolic signatures and shuttles in a human 3D neural cell model, namely the glutamine-glutamate-GABA shuttle...
2016: Scientific Reports
Tesfaye W Tefera, Yide Wong, Mallory E Barkl-Luke, Shyuan T Ngo, Nicola K Thomas, Tanya S McDonald, Karin Borges
There is increasing evidence that energy metabolism is disturbed in Amyotrophic Lateral Sclerosis (ALS) patients and animal models. Treatment with triheptanoin, the triglyceride of heptanoate, is a promising approach to provide alternative fuel to improve oxidative phosphorylation and aid ATP generation. Heptanoate can be metabolized to propionyl-CoA, which after carboxylation can produce succinyl-CoA and thereby re-fill the tricarboxylic acid (TCA) cycle (anaplerosis). Here we tested the hypothesis that treatment with triheptanoin prevents motor neuron loss and delays the onset of disease symptoms in female mice overexpressing the mutant human SOD1G93A (hSOD1G93A) gene...
2016: PloS One
Sowmyalakshmi Subramanian, Emily Ricci, Alfred Souleimanov, Donald L Smith
Salt stress is an important abiotic stressor affecting crop growth and productivity. Of the 20 percent of the terrestrial earth's surface available as agricultural land, 50 percent is estimated by the United Nations Environment Program to be salinized to the level that crops growing on it will be salt-stressed. Increased soil salinity has profound effects on seed germination and germinating seedlings as they are frequently confronted with much higher salinities than vigorously growing plants, because germination usually occurs in surface soils, the site of greatest soluble salt accumulation...
2016: PloS One
Jiao Meng, Baiyun Wang, Dingyu Liu, Tao Chen, Zhiwen Wang, Xueming Zhao
BACKGROUND: Succinate has been identified by the U.S. Department of Energy as one of the top 12 building block chemicals, which can be used as a specialty chemical in the agricultural, food, and pharmaceutical industries. Escherichia coli are now one of the most important succinate producing candidates. However, the stoichiometric maximum succinate yield under anaerobic conditions through the reductive branch of the TCA cycle is restricted by NADH supply in E. coli. RESULTS: In the present work, we report a rational approach to increase succinate yield by regulating NADH supply via pentose phosphate (PP) pathway and enhancing flux towards succinate...
2016: Microbial Cell Factories
H B Dong, L L Sun, R H Cong, S Y Tao, Y Q DuanMu, J Tian, Y D Ni, R Q Zhao
Feeding a high concentrate (HC) diet is a widely used strategy for supporting high milk yields, yet it may cause certain metabolic disorders. This study aimed to investigate the changes in milk production and hepatic metabolism in goats fed different proportions of concentrate in the diet for 10 weeks. In total, 12 mid-lactating goats were randomly assigned to an HC diet (65% concentrate of dry matter, n=6) or a low concentrate (LC) diet (35% concentrate of dry matter, n=6). Compared with LC, HC goats produced greater amounts of volatile fatty acids and produced more milk and milk lactose, fat and protein (P<0...
August 10, 2016: Animal: An International Journal of Animal Bioscience
Youngmin Kim, Mi-Jin Kwon, Jeong-Wook Choi, Min-Kyeong Lee, Chorong Kim, Jaehun Jung, Heny Aprianita, Heesop Nam, Taek-Jeong Nam
The aim of this study was to examine the anti-obesity effects of boiled tuna extract in C57BL/6N mice with obesity induced by a high-fat diet (HFD). We determined the anti-obesity effects of boiled tuna extract (100, 200, or 400 mg/kg) on the progression of HFD-induced obesity for 10 weeks. The mice were divided into 5 groups as follows: the normal diet (ND) group (n=10); the HFD group (n=10); the mice fed HFD and 100 mg/kg boiled tuna extract group (n=10); those fed a HFD and 200 mg/kg boiled tuna extract group (n=10); and those fed a HFD and 400 mg/kg boiled tuna extract group (n=10)...
October 2016: International Journal of Molecular Medicine
Michelle A C Reed, Christian Ludwig, Christopher M Bunce, Farhat L Khanim, Ulrich L Günther
BACKGROUND: The role of anaplerotic nutrient entry into the Krebs cycle via pyruvate carboxylase has been the subject of increased scrutiny and in particular whether this is dysregulated in cancer. Here, we use a tracer-based NMR analysis involving high-resolution (1)H-(13)C-HSQC spectra to assess site-specific label incorporation into a range of metabolite pools, including malate, aspartate and glutamate in the acute myeloid leukaemia cell line K562. We also determine how this is affected following treatment with the redeployed drug combination of the lipid-regulating drug bezafibrate and medroxyprogesterone (BaP)...
2016: Cancer & Metabolism
Q Hu, U Agarwal, B J Bequette
We aimed to quantify the rate of gluconeogenesis (GNG), non-essential amino-acid (NEAA) synthesis, and substrate partitioning to the Krebs cycle in embryonic (e) day e14 and e19 chicken embryos. An in ovo continuous tracer infusion approach was employed to test the hypotheses that GNG and NEAA synthesis in developing chicken embryo increases from e14 to e19. [(13)C6]Glucose or [(13)C3]glycerol was continuously infused (8 h) into the chorio-allantoic compartment of eggs on e14 and e19. Glucose entry rate, Cori cycling, and GNG were higher (P < 0...
August 2, 2016: Poultry Science
Qian Zhang, Sandra J Bertics, N Daniel Luchini, Heather M White
Metabolizable methionine (Met) concentrations can be increased by feeding rumen-protected dl-Met or the isopropyl ester of 2-hydroxy-4-(methylthio) butanoic acid (HMBi). Hepatic responses to increasing concentrations of metabolizable Met as a result of supplementation of different Met sources have not been comparatively examined. The objective of this experiment was to examine the regulation of key genes for Met metabolism, gluconeogenesis, and fatty acid oxidation in response to increasing concentrations of dl-Met or 2-hydroxy-4-(methylthio) butanoic acid (HMB) in bovine primary hepatocytes...
October 2016: Journal of Dairy Science
Huifeng Peng, Dong Wei, Gu Chen, Feng Chen
BACKGROUND: Microalgae are emerging as suitable feedstock for renewable biofuel production and providing a promising way to alleviate green house gas CO2. Characterizing the metabolic pathways involved in the biosynthesis of energy-rich compounds and their global regulation upon elevated CO2 is necessary to explore the mechanism underlying rapid growth and lipid accumulation, so as to realize the full potential of these organisms as energy resources. RESULTS: In the present study, 2 and 5 % CO2 increased growth rate and lipid accumulation in autotrophically cultured green alga Coccomyxa subellipsoidea C-169...
2016: Biotechnology for Biofuels
Ming-Zhe Ma, Yan Zhang, Ming-Zhe Weng, Shou-Hua Wang, Ye Hu, Zhao-Yuan Hou, Yi-Yu Qin, Wei Gong, Yong-Jie Zhang, Xiang Kong, Jian-Dong Wang, Zhi-Wei Quan
Long noncoding RNAs (lncRNA) are being implicated in the development of many cancers. Here, we report the discovery of a critical role for the lncRNA GCASPC in determining the progression of gallbladder cancer. Differentially expressed lncRNAs and mRNAs between gallbladder cancer specimens and paired adjacent nontumor tissues from five patients were identified and validated by an expression microarray analysis. Quantitative real-time PCR was used to measure GCASPC levels in tissues from 42 gallbladder cancer patients, and levels of GCASPC were confirmed further in a separate cohort of 89 gallbladder cancer patients...
September 15, 2016: Cancer Research
A Regassa, E Kiarie, J S Sands, M C Walsh, W K Kim, C M Nyachoti
Effects of substituting cornstarch with D-xylose on growth performance, nutrients digestibility, serum metabolites, and expression of select hepatic genes involved in glucose and lipid metabolism were investigated in broiler chickens. A total of 360 one-day-old male Ross chicks were fed 3 diets (n = 24; 5 chicks/cage) for 21 days. A control corn-soybean meal-based diet with 25% cornstarch was formulated to meet specifications. Two additional diets were formulated by substituting cornstarch with 5 or 15% D-xylose w/w...
July 21, 2016: Poultry Science
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