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https://www.readbyqxmd.com/read/28101749/twenty-seven-years-of-cerebral-pyruvate-recycling
#1
Sebastián Cerdán
Cerebral pyruvate recycling is a metabolic pathway deriving carbon skeletons and reducing equivalents from mitochondrial oxaloacetate and malate, to the synthesis of mitochondrial and cytosolic pyruvate, lactate and alanine. The pathway allows both, to provide the tricarboxylic acid cycle with pyruvate molecules produced from alternative substrates to glucose and, to generate reducing equivalents necessary for the operation of NADPH requiring processes. At the cellular level, pyruvate recycling involves the activity of malic enzyme, or the combined activities of phosphoenolpyruvate carboxykinase and pyruvate kinase, as well as of those transporters of the inner mitochondrial membrane exchanging the corresponding intermediates...
January 18, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28096234/glutamate-oxaloacetate-transaminase-enables-anaplerotic-refilling-of-tca-cycle-intermediates-in-stroke-affected-brain
#2
Cameron Rink, Surya Gnyawali, Richard Stewart, Seth Teplitsky, Hallie Harris, Sashwati Roy, Chandan K Sen, Savita Khanna
Ischemic stroke results in excessive release of glutamate, which contributes to neuronal cell death. Here, we test the hypothesis that otherwise neurotoxic glutamate can be productively metabolized by glutamate oxaloacetate transaminase (GOT) to maintain cellular energetics and protect the brain from ischemic stroke injury. The GOT-dependent metabolism of glutamate was studied in primary neural cells and in stroke-affected C57-BL6 mice using magnetic resonance spectroscopy and GC-MS. Extracellular Glu sustained cell viability under hypoglycemic conditions and increased GOT-mediated metabolism in vitro Correction of stroke-induced hypoxia using supplemental oxygen in vivo lowered Glu levels as measured by (1)H magnetic resonance spectroscopy...
January 17, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28092839/effect-and-mechanism-of-sorbus-pohuashanensis-hante-hedl-flavonoids-protect-against-arsenic-trioxide-induced-cardiotoxicity
#3
Xiaojin Yu, Zhenyu Wang, Zunpeng Shu, Zhengqing Li, Yuan Ning, Keli Yun, Haina Bai, Ruihai Liu, Wenli Liu
The cardiotoxicity of arsenic trioxide (ATO) limits its clinical application in cancer treatment. Evidences suggest that sorbus has antioxidant activity and its consumption has been linked with improved cardioprotection. In this study, we investigated the cardio-protective effect and mechanisms of Sorbus pohuashanensis (Hante) Hedl. flavonoids (SPF) against ATO in BALB/c mice and H9c2 cells. Eleven major flavonoids were confirmed by ultra-performance liquid chromatography electrospray ionization quadrupole time of flight mass spectrometry (UPLC-ESI-Q-TOF-MS)...
January 13, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28089748/bioaccumulation-of-lead-and-non-specific-immune-responses-in-white-shrimp-litopenaeus-vannamei-to-pb-exposure
#4
Yu-Sheng Wu, Shih-Ling Huang, Hsin-Chieh Chung, Fan-Hua Nan
In this study, we investigated organ accumulation and nonspecific immune response in white shrimp (Litopenaeus vannamei) that were exposed to various concentrations of lead (Pb) solution. The concentrations of Pb in the hepatopancreas, haemolymph, and muscle were measured moreover the total heamocyte count, phenoloxidase activity, O2(-) and physiological factors such as glutamic oxaloacetate transaminase (GOT), glutamic pyruvic transaminase (GPT), and haemolymph glucose were detected. The results showed that the hepatopancreas was the main organ of accumulation of Pb in white shrimp and the cumulative concentration of each organ was positively correlated with the experimental Pb concentration and immersion time...
January 12, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28080896/traumatic-foreign-body-pericarditis-in-a-toco-toucan-ramphastos-toco
#5
Mireia Máinez, Jorge Rosell, Roger Such, Teresa Cardona, Carles Juan-Sallés
An approximately 10-yr-old, captive-born female toco toucan ( Ramphastos toco ) was presented due to an acute onset of depression and apathy. On visual and physical examination, it showed an abnormal posture and dehydration, respectively. Serum biochemistry revealed hyperuricemia (39.4 mg/dl) and elevated glutamic oxaloacetic transaminase (GOT; 1,050 U/L). Radiographs demonstrated an enlargement of the cardiac silhouette. The bird died 7 days after presentation, despite treatment with enrofloxacin, allopurinol, a preparation of hepatorenal protectors, and complex B vitamins with dextrose...
December 2016: Journal of Zoo and Wildlife Medicine: Official Publication of the American Association of Zoo Veterinarians
https://www.readbyqxmd.com/read/28059425/metabolic-profiling-of-a-myalgic-encephalomyelitis-chronic-fatigue-syndrome-discovery-cohort-reveals-disturbances-in-fatty-acid-and-lipid-metabolism
#6
Arnaud Germain, David Ruppert, Susan M Levine, Maureen R Hanson
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) remains a continuum spectrum disease without biomarkers or simple objective tests, and therefore relies on a diagnosis from a set of symptoms to link the assortment of brain and body disorders to ME/CFS. Although recent studies show various affected pathways, the underlying basis of ME/CFS has yet to be established. In this pilot study, we compare plasma metabolic signatures in a discovery cohort, 17 patients and 15 matched controls, and explore potential metabolic perturbations as the aftermath of the complex interactions between genes, transcripts and proteins...
January 6, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28043922/reconstruction-of-a-genome-scale-metabolic-model-and-in-silico-analysis-of-the-polymalic-acid-producer-aureobasidium-pullulans-cctcc-m2012223
#7
Jun Feng, Jing Yang, Xiaorong Li, Meijin Guo, Bochu Wang, Shang-Tian Yang, Xiang Zou
Aureobasidium pullulans is a yeast-like fungus used for producing biopolymers e.g. polymalic acid (PMA) and pullulan. A high PMA producing strain, A. pullulans CCTCC M2012223, was isolated and sequenced in our previous study. To understand its metabolic performance, a genome-scale metabolic model, iZX637, consisting of 637 genes, 1347 reactions and 1133 metabolites, was reconstructed based on genome annotation and literature mining studies. The iZX637 model was validated by simulating cell growth, utilization of carbon and nitrogen sources, and gene essentiality analysis in A...
December 30, 2016: Gene
https://www.readbyqxmd.com/read/28043145/cytotoxic-effect-of-oxaloacetate-on-hepg2-human-hepatic-carcinoma-cells-via-apoptosis-and-ros-accumulation
#8
Y Jiao, L Ji, Y Kuang, Q Yang
Oxaloacetate (OA) is one of the intermediates of the Krebs cycle. In addition to its role in energy production, OA may have other effects on the cell. We report here that OA could have a cell type dependent cytotoxic effect on the human hepatic carcinoma cell line HepG2 through induction of apoptosis and reactive oxygen species (ROS) accumulation. In our study, OA decreased the viability and colony formation of HepG2 cells and induced cell death. Caspase-3 activity was increased, the pro-apoptotic protein Bax was up-regulated, and the anti-apoptotic protein Bcl-2 was down-regulated in OA-treated HepG2 cells indicating that apoptosis through the intrinsic pathway was involved in the cell death...
January 3, 2017: Neoplasma
https://www.readbyqxmd.com/read/27989324/mutations-in-mdh2-encoding-a-krebs-cycle-enzyme-cause-early-onset-severe-encephalopathy
#9
Samira Ait-El-Mkadem, Manal Dayem-Quere, Mirjana Gusic, Annabelle Chaussenot, Sylvie Bannwarth, Bérengère François, Emmanuelle C Genin, Konstantina Fragaki, Catharina L M Volker-Touw, Christelle Vasnier, Valérie Serre, Koen L I van Gassen, Françoise Lespinasse, Susan Richter, Graeme Eisenhofer, Cécile Rouzier, Fanny Mochel, Anne De Saint-Martin, Marie-Thérèse Abi Warde, Monique G M de Sain-van der Velde, Judith J M Jans, Jeanne Amiel, Ziga Avsec, Christian Mertes, Tobias B Haack, Tim Strom, Thomas Meitinger, Penelope E Bonnen, Robert W Taylor, Julien Gagneur, Peter M van Hasselt, Agnès Rötig, Agnès Delahodde, Holger Prokisch, Sabine A Fuchs, Véronique Paquis-Flucklinger
MDH2 encodes mitochondrial malate dehydrogenase (MDH), which is essential for the conversion of malate to oxaloacetate as part of the proper functioning of the Krebs cycle. We report bi-allelic pathogenic mutations in MDH2 in three unrelated subjects presenting with early-onset generalized hypotonia, psychomotor delay, refractory epilepsy, and elevated lactate in the blood and cerebrospinal fluid. Functional studies in fibroblasts from affected subjects showed both an apparently complete loss of MDH2 levels and MDH2 enzymatic activity close to null...
January 5, 2017: American Journal of Human Genetics
https://www.readbyqxmd.com/read/27988821/comparative-metabolomics-reveals-the-mechanism-of-avermectin-production-enhancement-by-s-adenosylmethionine
#10
Pingping Tian, Peng Cao, Dong Hu, Depei Wang, Jian Zhang, Lin Wang, Yan Zhu, Qiang Gao
It was found that S-adenosylmethionine (SAM) could effectively improve avermectin titer with 30-60 μg/mL addition to FH medium. To clearly elucidate the mechanism of SAM on intracellular metabolites of Streptomyces avermitilis, a GC-MS-based comparative metabolomics approach was carried out. First, 230 intracellular metabolites were identified and 14 of them remarkably influenced avermectin biosynthesis were discriminative biomarkers between non-SAM groups and SAM-treated groups by principal components analysis (PCA) and partial least squares (PLS)...
December 17, 2016: Journal of Industrial Microbiology & Biotechnology
https://www.readbyqxmd.com/read/27956466/plasma-amino-acid-levels-are-elevated-in-young-healthy-low-birth-weight-men-exposed-to-short-term-high-fat-overfeeding
#11
Amalie Ribel-Madsen, Lars I Hellgren, Charlotte Brøns, Rasmus Ribel-Madsen, Christopher B Newgard, Allan A Vaag
Low birth weight (LBW) individuals exhibit a disproportionately increased, incomplete fatty acid oxidation and a decreased glucose oxidation, compared with normal birth weight (NBW) individuals, and furthermore have an increased risk of developing insulin resistance and type 2 diabetes. We hypothesized that changes in amino acid metabolism may occur parallel to alterations in fatty acid and glucose oxidation, and could contribute to insulin resistance. Therefore, we measured fasting plasma levels of 15 individual or pools of amino acids in 18 LBW and 25 NBW men after an isocaloric control diet and after a 5-day high-fat, high-calorie diet...
December 2016: Physiological Reports
https://www.readbyqxmd.com/read/27943261/efavirenz-or-nevirapine-in-three-drug-combination-therapy-with-two-nucleoside-or-nucleotide-reverse-transcriptase-inhibitors-for-initial-treatment-of-hiv-infection-in-antiretroviral-na%C3%A3-ve-individuals
#12
REVIEW
Lawrence Mbuagbaw, Sara Mursleen, James H Irlam, Alicen B Spaulding, George W Rutherford, Nandi Siegfried
BACKGROUND: The advent of highly active antiretroviral therapy (ART) has reduced the morbidity and mortality due to HIV infection. The World Health Organization (WHO) ART guidelines focus on three classes of antiretroviral drugs, namely nucleoside or nucleotide reverse transcriptase inhibitors (NRTI), non-nucleoside reverse transcriptase inhibitors (NNRTI) and protease inhibitors. Two of the most common medications given as first-line treatment are the NNRTIs, efavirenz (EFV) and nevirapine (NVP)...
10, 2016: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/27943105/hypolipidemic-and-hypoglycemic-activities-of-a-oleanolic-acid-derivative-from-malva-parviflora-on-streptozotocin-induced-diabetic-mice
#13
Rosa Martha Pérez Gutiérrez
One new oleanolic acid derivative, 2α,3β,23α,29α tetrahydroxyolean-12(13)-en-28-oic acid (1) was isolated from the aerial parts of Malva parviflora. Their structure was characterized by spectroscopic methods. The hypolipidemic and hypoglycemic activities of 1 was analyzed in in streptozotocin (STZ)-nicotinamide-induced type 2 diabetes in mice (MD) and type 1 diabetes in streptozotocin-induced diabetic mice (SD). Triterpene was administered orally at doses of 20 mg/kg for 4 weeks. Organ weight, body weight, glucose, fasting insulin, cholesterol-related lipid profile parameters, glutamate oxaloacetate transaminase (SGOT), glutamate pyruvate transaminase (SGPT), serum alkaline phosphatase (SALP), glucokinase, hexokinase, glucose-6-phosphatase activities and glycogen in liver were measured after 4 weeks of treatment...
December 10, 2016: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/27929535/dual-targeting-of-glutaminase-1-and-thymidylate-synthase-elicits-death-synergistically-in-nsclc
#14
Jae-Seon Lee, Joon H Kang, Seon-Hyeong Lee, Dongwan Hong, Jaekyoung Son, Kyeong M Hong, Jaewhan Song, Soo-Youl Kim
Glutaminase 1 (GLS1) expression is increased in non-small cell lung cancer (NSCLC). GLS1 knockdown using siRNA or inhibition using bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl)ethyl sulfide (BPTES) induced cell cycle arrest with significant reduction of ATP level while levels of reactive oxygen species or glutathione were not affected in NSCLC cell lines. Recently we found that NSCLC significantly depends on cytosol NADH for ATP production. GLS1 remarkably contributes to ATP production through transferring cytosolic NADH into mitochondria via malate-aspartate shuttle by supply of glutamate in NSCLC...
December 8, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27917251/droplet-millifluidics-for-kinetic-study-of-transketolase
#15
A Pinsolle, F Charmantray, L Hecquet, F Sarrazin
We present a continuous-flow reactor at the millifluidic scale coupled with an online, non-intrusive spectroscopic monitoring method for determining the kinetic parameters of an enzyme, transketolase (TK) used in biocatalysis for the synthesis of polyols by carboligation. The millifluidic system used is based on droplet flow, a well-established method for kinetic chemical data acquisition. The TK assay is based on the direct quantitative measurement of bicarbonate ions released during the transketolase-catalysed reaction in the presence of hydroxypyruvic acid as the donor, thanks to an irreversible reaction: bicarbonate ions react with phosphoenolpyruvate (PEP) in the presence of PEP carboxylase as the first auxiliary enzyme...
November 2016: Biomicrofluidics
https://www.readbyqxmd.com/read/27914869/glycolysis-without-pyruvate-kinase-in-clostridium-thermocellum
#16
Daniel G Olson, Manuel Hörl, Tobias Fuhrer, Jingxuan Cui, Jilai Zhou, Marybeth I Maloney, Daniel Amador-Noguez, Liang Tian, Uwe Sauer, Lee R Lynd
The metabolism of Clostridium thermocellum is notable in that it assimilates sugar via the EMP pathway but does not possess a pyruvate kinase enzyme. In the wild type organism, there are three proposed pathways for conversion of phosphoenolpyruvate (PEP) to pyruvate, which differ in their cofactor usage. One path uses pyruvate phosphate dikinase (PPDK), another pathway uses the combined activities of PEP carboxykinase (PEPCK) and oxaloacetate decarboxylase (ODC). Yet another pathway, the malate shunt, uses the combined activities of PEPCK, malate dehydrogenase and malic enzyme...
January 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/27910779/amelioration-of-doxorubicin-induced-cardiac-and-renal-toxicity-by-oxycarotenoid-lutein-and-its-mechanism-of-action
#17
Edakkadath Raghavan Sindhu, Thattaruparambil Raveendran Nithya, Ponnamparambil Purushothaman Binitha, Ramadasan Kuttan
We set out to determine the effect of oxycarotenoid lutein on reducing cardiac and renal toxicity induced by doxorubicin (DXR). We started with oral administration in rats of lutein for 15 d before administering DXR (30 mg/kg body weight, intraperitoneally, in a single dose). Animals in all groups were sacrificed 24 h after DXR administration. Serum markers of cardiac injury lactate dehydrogenase, creatine phosphokinase, serum glutamate oxaloacetate transaminase, and serum glutamate pyruvate transaminase increased drastically after DXR but decreased after lutein treatment (p < 0...
2016: Journal of Environmental Pathology, Toxicology and Oncology
https://www.readbyqxmd.com/read/27908774/increased-incorporation-of-gaseous-co2-into-succinate-by-escherichia-coli-overexpressing-carbonic-anhydrase-and-phosphoenolpyruvate-carboxylase-genes
#18
Soohyun Park, Jae-Ung Lee, Sukhyeong Cho, Hyeonsoo Kim, Han Bin Oh, Seung Pil Pack, Jinwon Lee
Carbon dioxide (CO2) is an abundant and cheap carbon source that is partly responsible for global warming in the atmosphere. The objective of this study was to construct a recombinant E. coli strain that can show enhanced production of succinate derived from CO2. In this study, we confirmed the enhancement of utilization by analyzing succinate containing one carbon-13 ((13)C) derived from (13)CO2. Firstly, the carbonic anhydrase gene (SP(-)HCCA) derived from Hahella chejuensis KCTC 2396 was over-expressed to enhance carbon flux toward bicarbonate ion (HCO3(-)) synthesis in E...
January 10, 2017: Journal of Biotechnology
https://www.readbyqxmd.com/read/27890529/mass-spectrometry-analysis-shows-the-biosynthetic-pathways-supported-by-pyruvate-carboxylase-in-highly-invasive-breast-cancer-cells
#19
Phatchariya Phannasil, Israr-Ul H Ansari, Mahmoud El Azzouny, Melissa J Longacre, Khanti Rattanapornsompong, Charles F Burant, Michael J MacDonald, Sarawut Jitrapakdee
We recently showed that the anaplerotic enzyme pyruvate carboxylase (PC) is up-regulated in human breast cancer tissue and its expression is correlated with the late stages of breast cancer and tumor size [Phannasil et al., PloS One 10, e0129848, 2015]. In the current study we showed that PC enzyme activity is much higher in the highly invasive breast cancer cell line MDA-MB-231 than in less invasive breast cancer cell lines. We generated multiple stable PC knockdown cell lines from the MDA-MB-231 cell line and used mass spectrometry with (13)C6-glucose and (13)C5-glutamine to discern the pathways that use PC in support of cell growth...
February 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27885626/anaplerosis-for-glutamate-synthesis-in-the-neonate-and-in-adulthood
#20
Eva Brekke, Tora Sund Morken, Anne B Walls, Helle Waagepetersen, Arne Schousboe, Ursula Sonnewald
A central task of the tricarboxylic acid (TCA, Krebs, citric acid) cycle in brain is to provide precursors for biosynthesis of glutamate, GABA, aspartate and glutamine. Three of these amino acids are the partners in the intricate interaction between astrocytes and neurons and form the so-called glutamine-glutamate (GABA) cycle. The ketoacids α-ketoglutarate and oxaloacetate are removed from the cycle for this process. When something is removed from the TCA cycle it must be replaced to permit the continued function of this essential pathway, a process termed anaplerosis...
2016: Advances in Neurobiology
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