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https://www.readbyqxmd.com/read/28208702/the-glutamate-dehydrogenase-pathway-and-its-roles-in-cell-and-tissue-biology-in-health-and-disease
#1
REVIEW
Andreas Plaitakis, Ester Kalef-Ezra, Dimitra Kotzamani, Ioannis Zaganas, Cleanthe Spanaki
Glutamate dehydrogenase (GDH) is a hexameric enzyme that catalyzes the reversible conversion of glutamate to α-ketoglutarate and ammonia while reducing NAD(P)⁺ to NAD(P)H. It is found in all living organisms serving both catabolic and anabolic reactions. In mammalian tissues, oxidative deamination of glutamate via GDH generates α-ketoglutarate, which is metabolized by the Krebs cycle, leading to the synthesis of ATP. In addition, the GDH pathway is linked to diverse cellular processes, including ammonia metabolism, acid-base equilibrium, redox homeostasis (via formation of fumarate), lipid biosynthesis (via oxidative generation of citrate), and lactate production...
February 8, 2017: Biology
https://www.readbyqxmd.com/read/28168164/vdac-tubulin-an-anti-warburg-pro-oxidant-switch
#2
REVIEW
Eduardo N Maldonado
Aerobic enhanced glycolysis characterizes the Warburg phenotype. In cancer cells, suppression of mitochondrial metabolism contributes to maintain a low ATP/ADP ratio that favors glycolysis. We propose that the voltage-dependent anion channel (VDAC) located in the mitochondrial outer membrane is a metabolic link between glycolysis and oxidative phosphorylation in the Warburg phenotype. Most metabolites including respiratory substrates, ADP, and Pi enter mitochondria only through VDAC. Oxidation of respiratory substrates in the Krebs cycle generates NADH that enters the electron transport chain (ETC) to generate a proton motive force utilized to generate ATP and to maintain mitochondrial membrane potential (ΔΨ)...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28166989/dose-dependent-inhibition-of-uterine-contractility-by-nitric-oxide-a-potential-mechanism-underlying-persistent-breeding-induced-endometritis-in-the-mare
#3
Firdous A Khan, Tracey S Chenier, Coral L Murrant, Robert A Foster, Joanne Hewson, Elizabeth L Scholtz
Nitric oxide (NO) may have a role in persistent breeding-induced endometritis in mares through an inhibitory effect on uterine contractility. The objectives of this study were to test the effect of NO on spontaneous uterine contractility in-vitro and to evaluate whether this effect varied between the longitudinal and circular muscle layers of the uterus. Reproductive tracts were collected from eight euthanized non-pregnant mares (age 4-19 years; body weight 405-530 kg). Transrectal examination of the reproductive tract was performed before euthanasia to evaluate stage of the estrous cycle and presence of any apparent abnormality...
March 1, 2017: Theriogenology
https://www.readbyqxmd.com/read/28163219/probing-the-metabolic-phenotype-of-breast-cancer-cells-by-multiple-tracer-stable-isotope-resolved-metabolomics
#4
Andrew N Lane, Julie Tan, Yali Wang, Jun Yan, Richard M Higashi, Teresa W-M Fan
Breast cancers vary by their origin and specific set of genetic lesions, which gives rise to distinct phenotypes and differential response to targeted and untargeted chemotherapies. To explore the functional differences of different breast cell types, we performed Stable Isotope Resolved Metabolomics (SIRM) studies of one primary breast (HMEC) and three breast cancer cells (MCF-7, MDAMB-231, and ZR75-1) having distinct genotypes and growth characteristics, using (13)C6-glucose, (13)C-1+2-glucose, (13)C5,(15)N2-Gln, (13)C3-glycerol, and (13)C8-octanoate as tracers...
February 2, 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/28153450/tailored-liquid-chromatography-mass-spectrometry-analysis-improves-the-coverage-of-the-intracellular-metabolome-of-heparg-cells
#5
Matthias Cuykx, Noelia Negreira, Charlie Beirnaert, Nele Van den Eede, Robim Rodrigues, Tamara Vanhaecke, Kris Laukens, Adrian Covaci
Metabolomics protocols are often combined with Liquid Chromatography-Mass Spectrometry (LC-MS) using mostly reversed phase chromatography coupled to accurate mass spectrometry, e.g. quadrupole time-of-flight (QTOF) mass spectrometers to measure as many metabolites as possible. In this study, we optimised the LC-MS separation of cell extracts after fractionation in polar and non-polar fractions. Both phases were analysed separately in a tailored approach in four different runs (two for the non-polar and two for the polar-fraction), each of them specifically adapted to improve the separation of the metabolites present in the extract...
March 3, 2017: Journal of Chromatography. A
https://www.readbyqxmd.com/read/28153317/optimizing-2d-gas-chromatography-mass-spectrometry-for-robust-tissue-serum-and-urine-metabolite-profiling
#6
Zhanru Yu, Honglei Huang, Alexander Reim, Philip D Charles, Alan Northage, Dianne Jackson, Ian Parry, Benedikt M Kessler
Two-dimensional gas chromatography mass spectrometry (GCxGC-MS) is utilized to an increasing extent in biomedical metabolomics. Here, we established and adapted metabolite extraction and derivatization protocols for cell/tissue biopsy, serum and urine samples according to their individual properties. GCxGC-MS analysis revealed detection of ~600 molecular features from which 165 were characterized representing different classes such as amino acids, fatty acids, lipids, carbohydrates, nucleotides and small polar components of glycolysis and the Krebs cycle using electron impact (EI) spectrum matching and validation using external standard compounds...
April 1, 2017: Talanta
https://www.readbyqxmd.com/read/28139779/the-%C3%AE-and-%C3%AE-subunits-play-distinct-functional-roles-in-the-%C3%AE-2%C3%AE-%C3%AE-heterotetramer-of-human-nad-dependent-isocitrate-dehydrogenase
#7
Tengfei Ma, Yingjie Peng, Wei Huang, Yabing Liu, Jianping Ding
Human NAD-dependent isocitrate dehydrogenase existing as the α2βγ heterotetramer, catalyzes the decarboxylation of isocitrate into α-ketoglutarate in the Krebs cycle, and is allosterically regulated by citrate, ADP and ATP. To explore the functional roles of the regulatory β and γ subunits, we systematically characterized the enzymatic properties of the holoenzyme and the composing αβ and αγ heterodimers in the absence and presence of regulators. The biochemical and mutagenesis data show that αβ and αγ alone have considerable basal activity but the full activity of α2βγ requires the assembly and cooperative function of both heterodimers...
January 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28127420/permanent-draft-genome-of-thiobacillus-thioparus-dsm-505-t-an-obligately-chemolithoautotrophic-member-of-the-betaproteobacteria
#8
Lee P Hutt, Marcel Huntemann, Alicia Clum, Manoj Pillay, Krishnaveni Palaniappan, Neha Varghese, Natalia Mikhailova, Dimitrios Stamatis, Tatiparthi Reddy, Chris Daum, Nicole Shapiro, Natalia Ivanova, Nikos Kyrpides, Tanja Woyke, Rich Boden
Thiobacillus thioparus DSM 505(T) is one of first two isolated strains of inorganic sulfur-oxidising Bacteria. The original strain of T. thioparus was lost almost 100 years ago and the working type strain is Culture C(T) (=DSM 505(T) = ATCC 8158(T)) isolated by Starkey in 1934 from agricultural soil at Rutgers University, New Jersey, USA. It is an obligate chemolithoautotroph that conserves energy from the oxidation of reduced inorganic sulfur compounds using the Kelly-Trudinger pathway and uses it to fix carbon dioxide It is not capable of heterotrophic or mixotrophic growth...
2017: Standards in Genomic Sciences
https://www.readbyqxmd.com/read/28126513/inhibition-of-the-respiratory-chain-reactions-in-denitrifying-ebpr-biomass-under-simultaneous-presence-of-acetate-and-electron-acceptor
#9
Ilias Zafiriadis, Anastasios G Kapagiannidis, Spyridon Ntougias, Alexander Aivasidis
In this study, the deterioration of the typical EBPR (Enhanced Biological Phosphorus Removal) process due to the simultaneous presence of electron donor (external substrate) and electron acceptor (oxygen or nitrate) was investigated by using a PAOs (Polyphosphate Accumulating Organisms)-enriched biomass grown in a modified DEPHANOX system. Intracellular and extracellular constituents were monitored in batch tests under different electron donor and acceptor conditions and specific oxygen and nitrogen uptake rates were evaluated...
January 23, 2017: New Biotechnology
https://www.readbyqxmd.com/read/28116532/reversible-stress-softening-in-layered-rat-esophagus-in-vitro-after-potassium-chloride-activation
#10
Hongbo Jiang, Donghua Liao, Jingbo Zhao, Guixue Wang, Hans Gregersen
Significant stress softening recovery after potassium chloride (KCl) administration was previously demonstrated in the intact rat esophageal wall. The aim of this study is to investigate the effect of KCl activation on stress softening recovery in the separated mucosa-submucosa layer and muscle layer of rat esophagus. Three series of loading-unloading distensions were carried out on 10 rat esophagi where the two separated layers were distended at luminal pressure levels 0.5, 1.0 and 2.0 kPa. Numerous distension cycles were done in [Formula: see text]-free Krebs solution before and after activation with KCl (110 mmol) for 3 min in calcium-containing media...
January 23, 2017: Biomechanics and Modeling in Mechanobiology
https://www.readbyqxmd.com/read/28104508/exposure-to-high-levels-of-fumarate-and-succinate-leads-to-apoptotic-cytotoxicity-and-altered-global-dna-methylation-profiles-in-vitro
#11
Johannes F Wentzel, Angélique Lewies, Abel J Bronkhorst, Etresia van Dyk, Lissinda H du Plessis, Piet J Pretorius
In the Krebs cycle, succinate is oxidized to fumarate by succinate dehydrogenase (SDH), followed by the conversion of fumarate to malate by fumarate hydratase (FH). In cells with defective SDH and FH, the Krebs cycle is congested, respiration impaired and fumarate and succinate accumulates. Several studies have indicated that the accumulation of these substrates are associated with cytotoxicity and oncogenesis. High levels of succinate and fumarate induce hypoxia inducible factor (HIF1A) hydroxylases, leading to the activation of oncogenic HIF pathways...
January 16, 2017: Biochimie
https://www.readbyqxmd.com/read/28100843/pathophysiology-and-molecular-basis-of-selected-metabolic-abnormalities-in-huntington-s-disease
#12
Jolanta Krzysztoń-Russjan
Huntington's disease (HD) is an incurable, devastating neurodegenerative disease with a known genetic background and autosomally dominant inheritance pattern. HTT gene mutation (mHTT) is associated with polymorphic fragment elongation above 35 repeats of the CAG triplet. The mHTT product is an altered protein with a poly-Q elongated fragment, with the highest expression determined in the central nervous system (CNS) and with differentiated expression outside the CNS. A drastic loss of striatal and deeper layers of the cerebral cortex neurons was determined in the CNS, but muscle and body weight mass loss with dysfunction of many organs was also observed...
December 30, 2016: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/28098230/molecular-mechanism-of-the-allosteric-regulation-of-the-%C3%AE-%C3%AE-heterodimer-of-human-nad-dependent-isocitrate-dehydrogenase
#13
Tengfei Ma, Yingjie Peng, Wei Huang, Jianping Ding
Human NAD-dependent isocitrate dehydrogenase catalyzes the decarboxylation of isocitrate (ICT) into α-ketoglutarate in the Krebs cycle. It exists as the α2βγ heterotetramer composed of the αβ and αγ heterodimers. Previously, we have demonstrated biochemically that the α2βγ heterotetramer and αγ heterodimer can be allosterically activated by citrate (CIT) and ADP. In this work, we report the crystal structures of the αγ heterodimer with the γ subunit bound without or with different activators...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28075562/evidence-for-a-di-%C3%AE-oxo-diamond-core-in-the-mn-iv-fe-iv-activation-intermediate-of-ribonucleotide-reductase-from-chlamydia-trachomatis
#14
Ryan J Martinie, Elizabeth J Blaesi, Carsten Krebs, J Martin Bollinger, Alexey Silakov, Christopher J Pollock
High-valent iron and manganese complexes effect some of the most challenging biochemical reactions known, including hydrocarbon and water oxidations associated with the global carbon cycle and oxygenic photosynthesis, respectively. Their extreme reactivity presents an impediment to structural characterization, but their biological importance and potential chemical utility have, nevertheless, motivated extensive efforts toward that end. Several such intermediates accumulate during activation of class I ribonucleotide reductase (RNR) β subunits, which self-assemble dimetal cofactors with stable one-electron oxidants that serve to initiate the enzyme's free-radical mechanism...
January 27, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28073690/citrate-pathophysiology-and-metabolism
#15
REVIEW
Mehran Monchi
By chelating ionized calcium, citrate allows extracorporeal circuit anticoagulation without a bleeding risk for the patient. Citrate anticoagulation is also associated with a reduced activation of leucocytes and platelets. Citrate clearance by citric acid cycle (Krebs cycle) is not modified by renal failure, but is reduced by about 50% in patients with cirrhosis. Toxic effects of citrate result from a decrease in plasma ionized calcium of the patient. The first side effect is a prolongation of the QT interval...
December 30, 2016: Transfusion and Apheresis Science
https://www.readbyqxmd.com/read/28070280/surviving-winter-food-but-not-habitat-structure-prevents-crashes-in-cyclic-vole-populations
#16
Kaja Johnsen, Rudy Boonstra, Stan Boutin, Olivier Devineau, Charles J Krebs, Harry P Andreassen
Vole population cycles are a major force driving boreal ecosystem dynamics in northwestern Eurasia. However, our understanding of the impact of winter on these cycles is increasingly uncertain, especially because climate change is affecting snow predictability, quality, and abundance. We examined the role of winter weather and snow conditions, the lack of suitable habitat structure during freeze-thaw periods, and the lack of sufficient food as potential causes for winter population crashes. We live-trapped bank voles Myodes glareolus on 26 plots (0...
January 2017: Ecology and Evolution
https://www.readbyqxmd.com/read/28069660/antioxidant-treatment-attenuates-lactate-production-in-diabetic-nephropathy
#17
Christoffer Laustsen, Per Mose Nielsen, Thomas Stokholm Nørlinger, Haiyun Qi, Uffe Kjærgaard Pedersen, Lotte Bonde Bertelsen, Jakob Appel Østergaard, Allan Flyvbjerg, Jan Henrik Ardenkjær-Larsen, Fredrik Palm, Hans Stødkilde-Jørgensen
The early progression of diabetic nephropathy is notoriously difficult to detect and quantify before the occurrence of substantial histological damage. Recently, hyperpolarized [1-(13)C]pyruvate has demonstrated increased lactate production in the kidney early after the onset of diabetes, implying increased lactate dehydrogenase activity as a consequence of increased nicotinamide adenine dinucleotide substrate availability due to upregulation of the polyol pathway, i.e., pseudohypoxia. In this study, we investigated the role of oxidative stress in mediating these metabolic alterations using state-of-the-art hyperpolarized magnetic resonance (MR) imaging...
January 1, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28067713/widespread-down-regulation-of-cardiac-mitochondrial-and-sarcomeric-genes-in-patients-with-sepsis
#18
Scot J Matkovich, Belal Al Khiami, Igor R Efimov, Sarah Evans, Justin Vader, Ashwin Jain, Bernard H Brownstein, Richard S Hotchkiss, Douglas L Mann
OBJECTIVES: The mechanism(s) for septic cardiomyopathy in humans is not known. To address this, we measured messenger RNA alterations in hearts from patients who died from systemic sepsis, in comparison to changed messenger RNA expression in nonfailing and failing human hearts. DESIGN: Identification of genes with altered abundance in septic cardiomyopathy, ischemic heart disease, or dilated cardiomyopathy, in comparison to nonfailing hearts. SETTING: ICUs at Barnes-Jewish Hospital, St...
March 2017: Critical Care Medicine
https://www.readbyqxmd.com/read/28059791/mitochondrial-repair-effects-of-oxygen-treatment-on-alzheimer-s-disease-model-mice-revealed-by-quantitative-proteomics
#19
Hao Wang, Xiaoyu Hong, Yong Wang
Mitochondrial dysfunction plays a pivotal role in Alzheimer's disease (AD), even before signs of AD pathology are evident. Our previous research has shown that oxygen treatment can improve cognitive function in AD model mice. To address whether oxygen treatment is beneficial to mitochondrial biology, we analyzed differential expressions of hippocampal mitochondrial proteins in AD model mice given supplementary oxygen. Numerous respiratory chain, Kreb's cycle, and glycolysis proteins were upregulated significantly after oxygen treatment, suggesting that oxygen therapy can alleviate mitochondrial damage...
December 3, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28043145/cytotoxic-effect-of-oxaloacetate-on-hepg2-human-hepatic-carcinoma-cells-via-apoptosis-and-ros-accumulation
#20
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
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