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Pyruvate carboxylase

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https://www.readbyqxmd.com/read/29142828/metabolic-engineering-of-ustilago-trichophora-tz1-for-improved-malic-acid-production
#1
Thiemo Zambanini, Hamed Hosseinpour Tehrani, Elena Geiser, Christiane K Sonntag, Joerg M Buescher, Guido Meurer, Nick Wierckx, Lars M Blank
Ustilago trichophora RK089 has been found recently as a good natural malic acid producer from glycerol. This strain has previously undergone adaptive laboratory evolution for enhanced substrate uptake rate resulting in the strain U. trichophora TZ1. Medium optimization and investigation of process parameters enabled titers and rates that are able to compete with those of organisms overexpressing major parts of the underlying metabolic pathways. Metabolic engineering can likely further increase the efficiency of malate production by this organism, provided that basic genetic tools and methods can be established for this rarely used and relatively obscure species...
June 2017: Metabolic Engineering Communications
https://www.readbyqxmd.com/read/29136931/understanding-regulation-in-substrate-dependent-modulation-of-growth-and-production-of-alcohols-in-clostridium-sporogenes-ncim-2918-through-metabolic-network-reconstruction-and-flux-balance-analysis
#2
Mehak Kaushal, K Venkata Narayana Chary, Saumya Ahlawat, Basavaraj Palabhanvi, Gargi Goswami, Debasish Das
Flux Balance Analysis was performed for Clostridium sporogenes NCIM 2918 grown on sole glucose and glycerol or glucose-glycerol combinations at varied concentrations. During acidogenesis, glucose and glucose-glycerol combinations favored improved growth and butyric acid production. Glycerol fermentation was however marked by reduced growth and predominant ethanol synthesis. Further, with increase of glycerol fraction in glucose-glycerol blend, flux towards ethanol synthesis linearly increased with simultaneous decrease in butanol flux...
November 1, 2017: Bioresource Technology
https://www.readbyqxmd.com/read/29129786/mechanisms-by-which-a-very-low-calorie-diet-reverses-hyperglycemia-in-a-rat-model-of-type-2-diabetes
#3
Rachel J Perry, Liang Peng, Gary W Cline, Yongliang Wang, Aviva Rabin-Court, Joongyu D Song, Dongyan Zhang, Xian-Man Zhang, Yuichi Nozaki, Sylvie Dufour, Kitt Falk Petersen, Gerald I Shulman
Caloric restriction rapidly reverses type 2 diabetes (T2D), but the mechanism(s) of this reversal are poorly understood. Here we show that 3 days of a very-low-calorie diet (VLCD, one-quarter their typical intake) lowered plasma glucose and insulin concentrations in a rat model of T2D without altering body weight. The lower plasma glucose was associated with a 30% reduction in hepatic glucose production resulting from suppression of both gluconeogenesis from pyruvate carboxylase (VPC), explained by a reduction in hepatic acetyl-CoA content, and net hepatic glycogenolysis...
November 8, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/29052269/control-of-biotin-biosynthesis-in-mycobacteria-by-a-pyruvate-carboxylase-dependent-metabolic-signal
#4
Nathaniel Lazar, Allison Fay, Madhumitha Nandakumar, Kerry E Boyle, Joao Xavier, Kyu Rhee, Michael S Glickman
Biotin is an essential cofactor utilized by all domains of life, but only synthesized by bacteria, fungi and plants, making biotin biosynthesis a target for antimicrobial development. To understand biotin biosynthesis in mycobacteria, we executed a genetic screen in Mycobacterium smegmatis for biotin auxotrophs and identified pyruvate carboxylase (Pyc) as required for biotin biosynthesis. The biotin auxotrophy of the pyc::tn strain is due to failure to transcriptionally induce late stage biotin biosynthetic genes in low biotin conditions...
October 20, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/29047296/in%C3%A2-vivo-13-c-mrs-in-the-mouse-brain-at-14-1-tesla-and-metabolic-flux-quantification-under-infusion-of-1-6-13-c2-glucose
#5
Marta Lai, Bernard Lanz, Carole Poitry-Yamate, Jackeline F Romero, Corina M Berset, Cristina Cudalbu, Rolf Gruetter
In vivo (13)C magnetic resonance spectroscopy (MRS) enables the investigation of cerebral metabolic compartmentation while, e.g. infusing (13)C-labeled glucose. Metabolic flux analysis of (13)C turnover previously yielded quantitative information of glutamate and glutamine metabolism in humans and rats, while the application to in vivo mouse brain remains exceedingly challenging. In the present study, (13)C direct detection at 14.1 T provided highly resolved in vivo spectra of the mouse brain while infusing [1,6-(13)C2]glucose for up to 5 h...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/29024812/inhibition-of-pyruvate-carboxylase-by-1%C3%AE-25-dihydroxyvitamin-d-promotes-oxidative-stress-in-early-breast-cancer-progression
#6
Tomasz Wilmanski, Xuanzhu Zhou, Wei Zheng, Aparna Shinde, Shawn S Donkin, Michael Wendt, John R Burgess, Dorothy Teegarden
Maintaining reductive-oxidative (redox) balance is an essential feature in breast cancer cell survival, with cellular metabolism playing an integral role in maintaining redox balance through its supply of reduced NADPH. In the present studies, the effect of 1,25-dihydroxyvitamin D (1,25(OH)2D) on redox balance was investigated in early stages of breast cancer. Treatment with 1,25(OH)2D promoted oxidative stress in MCF10A-ras and MCF10A-ErbB2 breast epithelial cells, as measured by the decreased ratios of NADPH/NADP+ and reduced to oxidized glutathione (GSH/GSSG)...
October 9, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29024108/changes-in-hepatic-glucose-and-lipid-metabolism-related-parameters-in-domestic-pigeon-columba-livia-during-incubation-and-chick-rearing
#7
X P Wan, P Xie, Z Bu, X T Zou
This study aimed to evaluate the hepatic glucose and lipid metabolism-related parameters of adult male and female White King pigeons (Columba livia) during incubation and chick rearing. At day 4 (I4), 10 (I10) and 17 (I17) of incubation and day 1 (R1), 7 (R7), 15 (R15) and 25 (R25) of chick rearing, livers were sampled from six pigeons for each sex. Glycogen and fat contents, activities of glycolytic enzymes (hexokinase, HK; 6-phosphofructokinase, 6-PFK), and genes expressions of key enzymes involved in glycolysis (pyruvate kinase, PK; glucokinase, GK), gluconeogenesis (phosphoenolpyruvate carboxykinase cytosolic, PCK1; fructose-1,6-bisphosphatase, FBP1; glucose-6-phosphatase, G6Pase), fatty acid synthesis (fatty acid synthase, FAS; acetyl-CoA carboxylase, ACC) and fatty acid β-oxidation (carnitine palmitoyltransferase 1, CPT1; acyl-CoA 1, ACO) were measured...
October 12, 2017: Journal of Animal Physiology and Animal Nutrition
https://www.readbyqxmd.com/read/28988820/atf4-induced-metabolic-reprograming-is-a-synthetic-vulnerability-of-the-p62-deficient-tumor-stroma
#8
Juan F Linares, Thekla Cordes, Angeles Duran, Miguel Reina-Campos, Tania Valencia, Christopher S Ahn, Elias A Castilla, Jorge Moscat, Christian M Metallo, Maria T Diaz-Meco
Tumors undergo nutrient stress and need to reprogram their metabolism to survive. The stroma may play a critical role in this process by providing nutrients to support the epithelial compartment of the tumor. Here we show that p62 deficiency in stromal fibroblasts promotes resistance to glutamine deprivation by the direct control of ATF4 stability through its p62-mediated polyubiquitination. ATF4 upregulation by p62 deficiency in the stroma activates glucose carbon flux through a pyruvate carboxylase-asparagine synthase cascade that results in asparagine generation as a source of nitrogen for stroma and tumor epithelial proliferation...
September 27, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28986936/in-ovo-feeding-of-creatine-pyruvate-modulates-growth-performance-energy-reserves-and-mrna-expression-levels-of-gluconeogenesis-and-glycogenesis-enzymes-in-liver-of-embryos-and-neonatal-broilers
#9
M M Zhao, D Q Gong, T Gao, L Zhang, J L Li, P A Lv, L L Yu, F Gao, G H Zhou
The effects of in ovo feeding (IOF) of creatine pyruvate (CrPyr) on the growth performance, energy reserves and mRNA expression levels of gluconeogenesis and glycogenesis enzymes in liver of late-term embryos and neonatal broilers were investigated. After candling on 16 day of incubation, a total of 960 eggs were randomly assigned to three treatments: (i) non-injected control, (ii) saline group injected with 0.6 ml of 0.75% physiological saline and (iii) Creatine pyruvate group injected with 0.6 ml of physiological saline containing 12 mg CrPyr/egg...
October 7, 2017: Journal of Animal Physiology and Animal Nutrition
https://www.readbyqxmd.com/read/28986525/non-invasive-assessment-of-hepatic-mitochondrial-metabolism-by-positional-isotopomer-nmr-tracer-analysis-pinta
#10
Rachel J Perry, Liang Peng, Gary W Cline, Gina M Butrico, Yongliang Wang, Xian-Man Zhang, Douglas L Rothman, Kitt Falk Petersen, Gerald I Shulman
Hepatic mitochondria play a central role in the regulation of intermediary metabolism and maintenance of normoglycemia, and there is great interest in assessing rates of hepatic mitochondrial citrate synthase flux (V CS) and pyruvate carboxylase flux (V PC) in vivo. Here, we show that a positional isotopomer NMR tracer analysis (PINTA) method can be used to non-invasively assess rates of V CS and V PC fluxes using a combined NMR/gas chromatography-mass spectrometry analysis of plasma following infusion of [3-(13)C]lactate and glucose tracer...
October 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/28924963/combining-metabolic-and-process-engineering-strategies-to-improve-recombinant-glycoprotein-production-and-quality
#11
Eric Karengera, Yves Durocher, Gregory De Crescenzo, Olivier Henry
Increasing recombinant protein production while ensuring a high and consistent protein quality remains a challenge in mammalian cell culture process development. In this work, we combined a nutrient substitution approach with a metabolic engineering strategy that improves glucose utilization efficiency. This combination allowed us to tackle both lactate and ammonia accumulation and investigate on potential synergistic effects on protein production and quality. To this end, HEK293 cells overexpressing the pyruvate yeast carboxylase (PYC2) and their parental cells, both stably producing the therapeutic glycoprotein interferon α2b (IFNα2b), were cultured in media deprived of glutamine but containing chosen substitutes...
November 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28923861/mct1-inhibitor-azd3965-increases-mitochondrial-metabolism-facilitating-combination-therapy-and-noninvasive-magnetic-resonance-spectroscopy
#12
Mounia Beloueche-Babari, Slawomir Wantuch, Teresa Casals Galobart, Markella Koniordou, Harold G Parkes, Vaitha Arunan, Yuen-Li Chung, Thomas R Eykyn, Paul D Smith, Martin O Leach
Monocarboxylate transporters (MCT) modulate tumor cell metabolism and offer promising therapeutic targets for cancer treatment. Understanding the impact of MCT blockade on tumor cell metabolism may help develop combination strategies or identify pharmacodynamic biomarkers to support the clinical development of MCT inhibitors now in clinical trials. In this study, we assessed the impact of the MCT1 inhibitor AZD3965 on cancer cell metabolism in vitro and in vivo Exposing human lymphoma and colon carcinoma cells to AZD3965 increased MCT4-dependent accumulation of intracellular lactate, inhibiting monocarboxylate influx and efflux...
November 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/28893177/integrated-application-of-transcriptomics-and-metabolomics-provides-insights-into-glycogen-content-regulation-in-the-pacific-oyster-crassostrea-gigas
#13
Busu Li, Kai Song, Jie Meng, Li Li, Guofan Zhang
BACKGROUND: The Pacific oyster Crassostrea gigas is an important marine fishery resource, which contains high levels of glycogen that contributes to the flavor and the quality of the oyster. However, little is known about the molecular and chemical mechanisms underlying glycogen content differences in Pacific oysters. Using a homogeneous cultured Pacific oyster family, we explored these regulatory networks at the level of the metabolome and the transcriptome. RESULTS: Oysters with the highest and lowest natural glycogen content were selected for differential transcriptome and metabolome analysis...
September 11, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28867301/nonalcoholic-fatty-liver-disease-as-a-nexus-of-metabolic-and-hepatic-diseases
#14
REVIEW
Varman T Samuel, Gerald I Shulman
NAFLD is closely linked with hepatic insulin resistance. Accumulation of hepatic diacylglycerol activates PKC-ε, impairing insulin receptor activation and insulin-stimulated glycogen synthesis. Peripheral insulin resistance indirectly influences hepatic glucose and lipid metabolism by increasing flux of substrates that promote lipogenesis (glucose and fatty acids) and gluconeogenesis (glycerol and fatty acid-derived acetyl-CoA, an allosteric activator of pyruvate carboxylase). Weight loss with diet or bariatric surgery effectively treats NAFLD, but drugs specifically approved for NAFLD are not available...
August 29, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28808024/structural-and-functional-studies-of-pyruvate-carboxylase-regulation-by-cyclic-di-amp-in-lactic-acid-bacteria
#15
Philip H Choi, Thu Minh Ngoc Vu, Huong Thi Pham, Joshua J Woodward, Mark S Turner, Liang Tong
Cyclic di-3',5'-adenosine monophosphate (c-di-AMP) is a broadly conserved bacterial second messenger that has been implicated in a wide range of cellular processes. Our earlier studies showed that c-di-AMP regulates central metabolism in Listeria monocytogenes by inhibiting its pyruvate carboxylase (LmPC), a biotin-dependent enzyme with biotin carboxylase (BC) and carboxyltransferase (CT) activities. We report here structural, biochemical, and functional studies on the inhibition of Lactococcus lactis PC (LlPC) by c-di-AMP...
August 29, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28769797/over-expression-of-a-codon-optimized-yeast-cytosolic-pyruvate-carboxylase-pyc2-in-cho-cells-for-an-augmented-lactate-metabolism
#16
Sanjeev K Gupta, Ankit Sharma, Hiralal Kushwaha, Pratyoosh Shukla
Monoclonal antibodies are the most demanding biotherapeutic drugs now a days used for the cure of various critical illnesses. Chinese hamster ovary (CHO) cells are one of the main hosts used for the large scale production of these antibodies. However, the cell line and production processes are the key factors to determine the cost and affordability of these antibodies. The metabolic waste lactic acid and ammonium are accumulated during a cell culture process and adversely affects productivity as well as product quality...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28763459/metabolic-engineering-of-cho-cells-for-the-development-of-a-robust-protein-production-platform
#17
Sanjeev Kumar Gupta, Santosh K Srivastava, Ankit Sharma, Vaibhav H H Nalage, Darshita Salvi, Hiralal Kushwaha, Nikhil B Chitnis, Pratyoosh Shukla
Chinese hamster ovary (CHO) cells are the most preferred mammalian host used for the bio-pharmaceutical production. A major challenge in metabolic engineering is to balance the flux of the tuned heterogonous metabolic pathway and achieve efficient metabolic response in a mammalian cellular system. Pyruvate carboxylase is an important network element for the cytoplasmic and mitochondrial metabolic pathway and efficiently contributes in enhancing the energy metabolism. The lactate accumulation in cell culture can be reduced by re-wiring of the pyruvate flux in engineered cells...
2017: PloS One
https://www.readbyqxmd.com/read/28755262/physicochemical-and-microbial-responses-of-streptomyces-natalensis-hw-2-to-fungal-elicitor
#18
Dahong Wang, Lanlan Wei, Ying Zhang, Mengjuan Zhang, Shaobin Gu
The effects of fungal elicitor on the physicochemical and microbial responses of Streptomyces natalensis HW-2 were investigated. The results showed that the elicitor could decrease dry cell weight (DCW) by 17.7% and increase the utilization of glucose, while the curve of pH was not obviously altered. The elicitor enhanced the yield of natamycin from 1.33 to 2.49 g/L. The morphology of the colony and the mycelium treated with elicitor showed significant differences from that of control. The level of intracellular reactive oxygen species (ROS) increased to 333...
July 28, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28726641/a-plant-fungal-type-phosphoenolpyruvate-carboxykinase-located-in-the-parasite-mitochondrion-ensures-glucose-independent-survival-of-toxoplasma-gondii
#19
COMPARATIVE STUDY
Richard Nitzsche, Özlem Günay-Esiyok, Maximilian Tischer, Vyacheslav Zagoriy, Nishith Gupta
Toxoplasma gondii is considered to be one of the most successful intracellular pathogens, because it can reproduce in varied nutritional milieus, encountered in diverse host cell types of essentially any warm-blooded organism. Our earlier work demonstrated that the acute (tachyzoite) stage of T. gondii depends on cooperativity of glucose and glutamine catabolism to meet biosynthetic demands. Either of these two nutrients can sustain the parasite survival; however, what determines the metabolic plasticity has not yet been resolved...
September 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28718833/coconut-oil-aggravates-pressure-overload-induced-cardiomyopathy-without-inducing-obesity-systemic-insulin-resistance-or-cardiac-steatosis
#20
Ilayaraja Muthuramu, Ruhul Amin, Andrey Postnov, Mudit Mishra, Frank Jacobs, Olivier Gheysens, Paul P Van Veldhoven, Bart De Geest
Studies evaluating the effects of high-saturated fat diets on cardiac function are most often confounded by diet-induced obesity and by systemic insulin resistance. We evaluated whether coconut oil, containing C12:0 and C14:0 as main fatty acids, aggravates pressure overload-induced cardiomyopathy induced by transverse aortic constriction (TAC) in C57BL/6 mice. Mortality rate after TAC was higher (p < 0.05) in 0.2% cholesterol 10% coconut oil diet-fed mice than in standard chow-fed mice (hazard ratio 2.32, 95% confidence interval 1...
July 18, 2017: International Journal of Molecular Sciences
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