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Lactate AND NAD

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https://www.readbyqxmd.com/read/27909649/in-silico-profiling-of-cell-growth-and-succinate-production-in-escherichia-coli-nzn111
#1
Xingxing Jian, Ningchuan Li, Cheng Zhang, Qiang Hua
BACKGROUND: Succinic acid is a valuable product due to its wide-ranging utilities. To improve succinate production and reduce by-products formation, Escherichia coli NZN111 was constructed by insertional inactivation of lactate dehydrogenase (LDH) and pyruvate formate lyase (PFL) encoded by the genes ldhA and pflB, respectively. However, this double-deletion mutant is incapable of anaerobically growing on glucose in rich or minimal medium even with acetate supplementation. A widespread hold view is that the inactivation of NADH-dependent LDH limits the regeneration of NAD(+) and consequently disables proper growth under anaerobic conditions...
2016: Bioresources and Bioprocessing
https://www.readbyqxmd.com/read/27893829/sansevieria-roxburghiana-schult-schult-f-family-asparagaceae-attenuates-type-2-diabetes-and-its-associated-cardiomyopathy
#2
Niloy Bhattacharjee, Ritu Khanra, Tarun K Dua, Susmita Das, Bratati De, M Zia-Ul-Haq, Vincenzo De Feo, Saikat Dewanjee
BACKGROUND: Sansevieria roxburghiana Schult. & Schult. F. (Family: Asparagaceae) rhizome has been claimed to possess antidiabetic activity in the ethno-medicinal literature in India. Therefore, present experiments were carried out to explore the protective role of edible (aqueous) extract of S. roxburghiana rhizome (SR) against experimentally induced type 2 diabetes mellitus (T2DM) and its associated cardiomyopathy in Wistar rats. METHODS: SR was chemically characterized by GC-MS analysis...
2016: PloS One
https://www.readbyqxmd.com/read/27890529/mass-spectrometry-analysis-shows-the-biosynthetic-pathways-supported-by-pyruvate-carboxylase-in-highly-invasive-breast-cancer-cells
#3
Phatchariya Phannasil, Israr-Ul H Ansari, Mahmoud El Azzouny, Melissa J Longacre, Khanti Rattanapornsompong, Charles F Burant, Sarawut Jitrapakdee, Michael J MacDonald
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...
November 23, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27883243/alternative-mechanistic-strategy-for-enzyme-catalysis-in-a-ni-dependent-lactate-racemase-lara-intermediate-destabilization-by-the-cofactor
#4
Xiaoyong Zhang, Lung Wa Chung
Recently, a lactate racemase was discovered as a new Ni-dependent enzyme with a unique tethered NAD-like cofactor. We report the first computational study aimed at deciphering the previously unclear role of the Ni-tethered cofactor in reactions of lactate racemase. Our calculations revealed that the cofactor increases the dehydrogenation barriers. The formation of a metastable NADH-like pyruvate intermediate and two nearby histidine bases are proposed as the key factors in the racemization reaction. Such destabilization of intermediates by the cofactor is uncommon in enzymatic catalysis...
November 24, 2016: Chemistry: a European Journal
https://www.readbyqxmd.com/read/27798266/focally-perfused-succinate-potentiates-brain-metabolism-in-head-injury-patients
#5
Ibrahim Jalloh, Adel Helmy, Duncan J Howe, Richard J Shannon, Peter Grice, Andrew Mason, Clare N Gallagher, Matthew G Stovell, Susan van der Heide, Michael P Murphy, John D Pickard, David K Menon, T Adrian Carpenter, Peter J Hutchinson, Keri Lh Carpenter
Following traumatic brain injury, complex cerebral energy perturbations occur. Correlating with unfavourable outcome, high brain extracellular lactate/pyruvate ratio suggests hypoxic metabolism and/or mitochondrial dysfunction. We investigated whether focal administration of succinate, a tricarboxylic acid cycle intermediate interacting directly with the mitochondrial electron transport chain, could improve cerebral metabolism. Microdialysis perfused disodium 2,3-(13)C2 succinate (12 mmol/L) for 24 h into nine sedated traumatic brain injury patients' brains, with simultaneous microdialysate collection for ISCUS analysis of energy metabolism biomarkers (nine patients) and nuclear magnetic resonance of (13)C-labelled metabolites (six patients)...
October 17, 2016: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/27769837/ligand-binding-phenomena-that-pertain-to-the-metabolic-function-of-renalase
#6
Brett A Beaupre, Joseph V Roman, Matthew R Hoag, Kathleen M Meneely, Nicholas R Silvaggi, Audrey L Lamb, Graham R Moran
Renalase catalyzes the oxidation of isomers of β-NAD(P)H that carry the hydride in the 2 or 6 positions of the nicotinamide base to form β-NAD(P)(+). This activity is thought to alleviate inhibition of multiple β-NAD(P)-dependent enzymes of primary and secondary metabolism by these isomers. Here we present evidence for a variety of ligand binding phenomena relevant to the function of renalase. We offer evidence of the potential for primary metabolism inhibition with structures of malate dehydrogenase and lactate dehydrogenase bound to the 6-dihydroNAD isomer...
October 18, 2016: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/27759041/cytoplasmic-proliferating-cell-nuclear-antigen-connects-glycolysis-and-cell-survival-in-acute-myeloid-leukemia
#7
Delphine Ohayon, Alessia De Chiara, Nicolas Chapuis, Céline Candalh, Julie Mocek, Jean-Antoine Ribeil, Lamya Haddaoui, Norbert Ifrah, Olivier Hermine, Frédéric Bouillaud, Philippe Frachet, Didier Bouscary, Véronique Witko-Sarsat
Cytosolic proliferating cell nuclear antigen (PCNA), a scaffolding protein involved in DNA replication, has been described as a key element in survival of mature neutrophil granulocytes, which are non-proliferating cells. Herein, we demonstrated an active export of PCNA involved in cell survival and chemotherapy resistance. Notably, daunorubicin-resistant HL-60 cells (HL-60R) have a prominent cytosolic PCNA localization due to increased nuclear export compared to daunorubicin-sensitive HL-60 cells (HL-60S)...
October 19, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27708428/gsf2-deletion-increases-lactic-acid-production-by-alleviating-glucose-repression-in-saccharomyces-cerevisiae
#8
Seung-Ho Baek, Eunice Y Kwon, Seon-Young Kim, Ji-Sook Hahn
Improving lactic acid (LA) tolerance is important for cost-effective microbial production of LA under acidic fermentation conditions. Previously, we generated LA-tolerant D-LA-producing S. cerevisiae strain JHY5310 by laboratory adaptive evolution of JHY5210. In this study, we performed whole genome sequencing of JHY5310, identifying four loss-of-function mutations in GSF2, SYN8, STM1, and SIF2 genes, which are responsible for the LA tolerance of JHY5310. Among the mutations, a nonsense mutation in GSF2 was identified as the major contributor to the improved LA tolerance and LA production in JHY5310...
October 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27671200/enzymatic-and-thermodynamic-profiles-of-a-heterotetramer-lactate-dehydrogenase-isozyme-in-swine
#9
Tatsufumi Goto, Kotomi Sugawara, Shigeyoshi Nakamura, Shun-Ichi Kidokoro, Hideki Wakui, Wataru Nunomura
Lactate dehydrogenase (LDH) is a glycolytic enzyme that catalyzes the final step of glycolysis and produces NAD(+). In somatic cells, LDH forms homotetramers and heterotetramers that are encoded by two different genes: LDHA (skeletal muscle type, M) and LDHB (heart type, H). Analysis of LDH isozymes is important for understanding the physiological role of homotetramers and heterotetramers and for optimizing inhibition of their enzymatic activity as it may result in distinct effects. Previously, we reported that hydroxychloroquine (HCQ) inhibited LDH activity, but we did not examine isozyme specificity...
October 28, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27641904/metabolic-profile-of-1-5-diaminopentane-producing-corynebacterium-glutamicum-under-scale-down-conditions-blueprint-for-robustness-to-bioreactor-inhomogeneities
#10
Michael H Limberg, Julia Schulte, Tita Aryani, Regina Mahr, Meike Baumgart, Michael Bott, Wolfgang Wiechert, Marco Oldiges
Performance losses during scale-up are described since decades, but are still one of the major obstacles for industrial bioprocess development. Consequently, robustness to inhomogeneous cultivation environments is an important quality of industrial production organisms. Especially, Corynebacterium glutamicum was proven to have an outstanding resistance against rapid changes of oxygen and substrate availability as occurring in industrial scale bioreactors. This study focuses on the identification of metabolic key mechanisms for this robustness to get a deeper insight and provide future targets for process orientated strain development...
September 19, 2016: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/27641753/thymus-vulgaris-alleviates-uvb-irradiation-induced-skin-damage-via-inhibition-of-mapk-ap-1-and-activation-of-nrf2-are-antioxidant-system
#11
Zhengwang Sun, Sang Yong Park, Eunson Hwang, Mengyang Zhang, Seul A Seo, Pei Lin, Tae-Hoo Yi
Solar ultraviolet (UV) radiation-induced reactive oxidative species is mainly responsible for the development of photoageing. Rosmarinic acid was one of the main bioactive components detected in Thymus vulgaris (TV) we extracted. In this study, UVB-induced skin damages have been shown to be ameliorated by treatment with TV in hairless mice (HR-1) skin, demonstrated by decreased matrix metalloproteinases (MMPs) and increased collagen production. However, the underlying molecular mechanism on which TV acted was unclear...
September 19, 2016: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/27624811/a-rapid-and-efficient-luminescence-based-method-for-assaying-phosphoglycosyltransferase-enzymes
#12
Debasis Das, Marthe T C Walvoort, Vinita Lukose, Barbara Imperiali
Phosphoglycosyltransferases (PGTs) are families of integral membrane proteins with intriguingly diverse architectures. These enzymes function to initiate many important biosynthetic pathways including those leading to peptidoglycan, N-linked glycoproteins and lipopolysaccharide O-antigen. In spite of tremendous efforts, characterization of these enzymes remains a challenge not only due to the inherent difficulties associated with the purification of integral membrane proteins but also due to the limited availability of convenient assays...
September 14, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27622334/lactate-dehydrogenase-b-controls-lysosome-activity-and-autophagy-in-cancer
#13
Lucie Brisson, Piotr Bański, Martina Sboarina, Coralie Dethier, Pierre Danhier, Marie-Joséphine Fontenille, Vincent F Van Hée, Thibaut Vazeille, Morgane Tardy, Jorge Falces, Caroline Bouzin, Paolo E Porporato, Raphaël Frédérick, Carine Michiels, Tamara Copetti, Pierre Sonveaux
Metabolic adaptability is essential for tumor progression and includes cooperation between cancer cells with different metabolic phenotypes. Optimal glucose supply to glycolytic cancer cells occurs when oxidative cancer cells use lactate preferentially to glucose. However, using lactate instead of glucose mimics glucose deprivation, and glucose starvation induces autophagy. We report that lactate sustains autophagy in cancer. In cancer cells preferentially to normal cells, lactate dehydrogenase B (LDHB), catalyzing the conversion of lactate and NAD(+) to pyruvate, NADH and H(+), controls lysosomal acidification, vesicle maturation, and intracellular proteolysis...
September 12, 2016: Cancer Cell
https://www.readbyqxmd.com/read/27618187/lactate-metabolism-is-associated-with-mammalian-mitochondria
#14
Ying-Jr Chen, Nathaniel G Mahieu, Xiaojing Huang, Manmilan Singh, Peter A Crawford, Stephen L Johnson, Richard W Gross, Jacob Schaefer, Gary J Patti
It is well established that lactate secreted by fermenting cells can be oxidized or used as a gluconeogenic substrate by other cells and tissues. It is generally assumed, however, that within the fermenting cell itself, lactate is produced to replenish NAD(+) and then is secreted. Here we explore the possibility that cytosolic lactate is metabolized by the mitochondria of fermenting mammalian cells. We found that fermenting HeLa and H460 cells utilize exogenous lactate carbon to synthesize a large percentage of their lipids...
November 2016: Nature Chemical Biology
https://www.readbyqxmd.com/read/27616477/naxe-mutations-disrupt-the-cellular-nad-p-hx-repair-system-and-cause-a-lethal-neurometabolic-disorder-of-early-childhood
#15
Laura S Kremer, Katharina Danhauser, Diran Herebian, Danijela Petkovic Ramadža, Dorota Piekutowska-Abramczuk, Annette Seibt, Wolfgang Müller-Felber, Tobias B Haack, Rafał Płoski, Klaus Lohmeier, Dominik Schneider, Dirk Klee, Dariusz Rokicki, Ertan Mayatepek, Tim M Strom, Thomas Meitinger, Thomas Klopstock, Ewa Pronicka, Johannes A Mayr, Ivo Baric, Felix Distelmaier, Holger Prokisch
To safeguard the cell from the accumulation of potentially harmful metabolic intermediates, specific repair mechanisms have evolved. APOA1BP, now renamed NAXE, encodes an epimerase essential in the cellular metabolite repair for NADHX and NADPHX. The enzyme catalyzes the epimerization of NAD(P)HX, thereby avoiding the accumulation of toxic metabolites. The clinical importance of the NAD(P)HX repair system has been unknown. Exome sequencing revealed pathogenic biallelic mutations in NAXE in children from four families with (sub-) acute-onset ataxia, cerebellar edema, spinal myelopathy, and skin lesions...
October 6, 2016: American Journal of Human Genetics
https://www.readbyqxmd.com/read/27561726/assessment-of-metformin-induced-changes-in-cardiac-and-hepatic-redox-state-using-hyperpolarized-1-13c-pyruvate
#16
Andrew Jm Lewis, Jack Jj Miller, Chloe McCallum, Oliver J Rider, Stefan Neubauer, Lisa C Heather, Damian J Tyler
Metformin improves cardiovascular outcomes in type 2 diabetes, but its exact mechanisms of action remain controversial. We used hyperpolarized [1-(13)C]pyruvate magnetic resonance spectroscopy to determine the effects of metformin treatment upon heart and liver pyruvate metabolism in rats in vivo Both oral treatment for four weeks and a single intravenous metformin infusion significantly increased the cardiac [1-(13)C]lactate:[1-(13)C]pyruvate ratio, but had no effect on the [1-(13)C]bicarbonate + (13)CO2:[1-(13)C]pyruvate ratio, an index of pyruvate dehydrogenase flux...
August 25, 2016: Diabetes
https://www.readbyqxmd.com/read/27544614/regulation-of-crayfish-orconectes-virilis-tail-muscle-lactate-dehydrogenase-ldh-in-response-to-anoxic-conditions-is-associated-with-alterations-in-phosphorylation-patterns
#17
Stuart R Green, Kenneth B Storey
Lactate dehydrogenase (LDH), the terminal enzyme of anaerobic glycolysis, has a crucial role in sustaining ATP production by glycolysis during periods of anoxia via regenerating NAD(+) through the production of lactate. The present study examined the effects of prolonged (20h) anoxic submergence on LDH from the tail muscle of an anoxia-tolerant crayfish (Orconectes virilis). LDH was purified to homogeneity from tail muscle of both aerobic control and anoxic crayfish in a three step process. Analysis of the kinetic parameters and the stability of LDH showed that the Vmax in the pyruvate-reducing direction was significantly higher for the enzyme from anoxic crayfish whereas in the lactate-oxidizing direction the Vmax was significantly higher for the control enzyme...
August 17, 2016: Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology
https://www.readbyqxmd.com/read/27513948/impact-of-cyclometalated-ruthenium-ii-complexes-on-lactate-dehydrogenase-activity-and-cytotoxicity-in-gastric-and-colon-cancer-cells
#18
Hugo Rico Bautista, Rafael Omar Saavedra Díaz, Longzhu Q Shen, Christophe Orvain, Christian Gaiddon, Ronan Le Lagadec, Alexander D Ryabov
Lactate dehydrogenase (LDH) is a redox enzyme often overexpressed in cancer cells allowing their survival in stressful metabolic tumor environment. Ruthenium(II) complexes have been shown to impact on the activity of purified horseradish peroxidase and glucose oxidase but the physiological relevance remains unclear. In this study we investigated how ruthenium complexes impact on the activity of LDH in vitro and in cancer cells and performed a comparative study using polypyridine ruthenium(II) complex [Ru(bpy)3](2+) (1) and its structurally related cyclometalated 2-phenylpyridinato counterpart [Ru(phpy)(bpy)2](+) (2) (bpy=2,2'-bipyridine, phpyH=2-phenylpyridine)...
July 26, 2016: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/27506262/changes-in-milk-performance-and-hepatic-metabolism-in-mid-lactating-dairy-goats-after-being-fed-a-high-concentrate-diet-for-10-weeks
#19
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
https://www.readbyqxmd.com/read/27461009/adverse-effects-of-anti-tuberculosis-drugs-on-hepg2-cell-bioenergetics
#20
E Elmorsy, S M Attalla, E Fikry, A Kocon, R Turner, D Christie, A Warren, L L Nwidu, W G Carter
Tuberculosis (TB) is an intractable chronic infection. Disease treatment with anti-TB drugs remains challenging due to drug-induced hepatotoxicity. The toxicity of the anti-TB drugs rifampicin (RIF), isoniazid (INH) and pyrazinamide (PZA) either alone or in combination was investigated in HepG2 cells. Assays of intracellular adenosine triphosphate (ATP) levels at 4-, 24- and 48-h post-exposure to gradient concentrations of RIF, INH and PZA were conducted. Drug-induced effects on mitochondrial membrane potential (MMP), mitochondrial complex I and complex III activity, nicotinamide adenine dinucleotide (NAD(+)) levels and cellular lactate production were assessed...
July 26, 2016: Human & Experimental Toxicology
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