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Lactate AND NAD

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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/28159812/right-ventricular-metabolism-during-veno-arterial-extracorporeal-membrane-oxygenation-in-immature-swine-heart-in-vivo
#2
Masaki Kajimoto, Dolena R Ledee, Nancy G Isern, Michael A Portman
Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) provides hemodynamic rescue for patients encountering right or left ventricular (RV or LV) decompensation, particularly after surgery for congenital heart defects. ECMO, supported metabolically by parenteral nutrition, provides reductions in myocardial work and energy demand and therefore enhances functional recovery. The RV must often assume systemic ventricular pressures and function upon weaning from VA-ECMO. However the substrate utilization responses of the RV to VA-ECMO or stimulation are unknown...
February 3, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28150419/misconceptions-regarding-basic-thermodynamics-and-enzyme-kinetics-have-led-to-erroneous-conclusions-regarding-the-metabolic-importance-of-lactate-dehydrogenase-isoenzyme-expression
#3
REVIEW
Lasse K Bak, Arne Schousboe
Lactate dehydrogenase (LDH) catalyzes the interconversion of pyruvate and lactate involving the coenzyme NAD(+) . Part of the foundation for the proposed shuttling of lactate from astrocytes to neurons during brain activation is the differential distribution of LDH isoenzymes between the two cell types. In this short review, we outline the basic kinetic properties of the LDH isoenzymes expressed in neurons and astrocytes, and argue that the distribution of LDH isoenzymes does not in any way govern directional flow of lactate between the two cellular compartments...
February 2, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28121062/exposure-to-15-oxygen-in-vivo-up-regulates-cardioprotective-sur2a-without-affecting-erk1-2-and-akt-a-crucial-role-for-ampk
#4
Khaja Shameem Mohammed Abdul, Sofija Jovanović, Aleksandar Jovanović
SUR2A is an 'atypical' ABC protein that forms sarcolemmal ATP-sensitive K(+) (KATP ) channels by binding to inward rectifier Kir6.2. Manipulation with SUR2A levels has been suggested to be a promising therapeutic strategy against ischaemic heart diseases and other diseases where increased heart resistance to stress is beneficial. Some years ago, it has been reported that high-altitude residents have lower mortality rates for ischaemic heart disease. The purpose of this study was to determine whether SUR2A is regulated by mild-to-severe hypoxic conditions (15% oxygen; oxygen tension equivalent to 3000 m above sea level) and elucidate the underlying mechanism...
January 25, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28108222/diquat-induced-cellular-pyridine-nucleotide-redox-changes-and-alteration-of-metabolic-enzyme-activities-in-colonic-carcinoma-cells
#5
Magdalena L Circu, Ronald E Maloney, Tak Yee Aw
Previously we have shown that the redox cycler menadione (MQ) induced cellular pyridine nucleotide redox imbalance that was linked to a decrease in aerobic glycolysis and perturbation of the mitochondrial respiratory activity due to the redox cycling of the compound; these processes were potentiated by low glucose. In this study, we investigated how colonic epithelial cells maintained pyridine nucleotide (NAD(+)/NADH and NADP(+)/NADPH) redox homeostasis upon acute metabolic variation and exposure to the redox cycling diquat (DQ)...
February 25, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28093125/hairpin-stabilized-fluorescent-silver-nanoclusters-for-quantitative-detection-of-nad-and-monitoring-nad-nadh-based-enzymatic-reactions
#6
Priyamvada Jain, Babina Chakma, Sanjukta Patra, Pranab Goswami
A set of 90 mer long ssDNA candidates, with different degrees of cytosine (C-levels) (% and clusters) was analyzed for their function as suitable Ag-nanocluster (AgNC) nucleation scaffolds. The sequence (P4) with highest C-level (42.2%) emerged as the only candidate supporting the nucleation process as evident from its intense fluorescence peak at λ660 nm. Shorter DNA subsets derived from P4 with only stable hairpin structures could support the AgNC formation. The secondary hairpin structures were confirmed by PAGE, and CD studies...
March 1, 2017: Analytica Chimica Acta
https://www.readbyqxmd.com/read/28087461/low-glucose-stress-decreases-cellular-nadh-and-mitochondrial-atp-in-colonic-epithelial-cancer-cells-influence-of-mitochondrial-substrates
#7
Magdalena L Circu, Ronald E Maloney, Tak Yee Aw
In this study, we investigated how colonic epithelial cells maintained pyridine nucleotide (NADH/NAD(+)) redox homeostasis upon acute metabolic variation imposed by glucose deprivation or supplementation with mitochondrial substrates, succinate and malate/glutamate (M/G). Our results showed that low glucose caused cellular NADH/NAD(+) redox imbalance that diminished lactate dehydrogenase (LDH) activity and resulted in lower lactate contents. The concurrent activation of malic enzyme (ME) suggested a role for malate in preserving cellular pyruvate that remained unchanged at low glucose...
February 25, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28079261/effect-of-parthanatos-on-ropivacaine-induced-damage-in-sh-sy5y-cells
#8
Ting Zheng, Chun-Ying Zheng, Xiao-Chun Zheng, Ruo-Guang Zhao, Yan-Qing Chen
Ropivacaine is one of the most common but toxic local anesthetics, and the mechanisms underlying its neurotoxicity are still largely unknown. This study was conducted to prepare a ropivacaine-induced neuronal injury model and research the effects of ropivacaine on PARP-1 activation and NAD(+) depletion. The cell death and apoptosis of ropivacaine-induced SH-SY5Y cells were detected with flow cytometry. The lactate dehydrogenase cycling reaction measured the NAD(+) level, and Western blots were used to analyze the expression levels of PARP-1 and AIF after ropivacaine treatments with different concentrations and durations...
January 12, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28062235/new-approach-to-biosensing-of-co-enzyme-nicotinamide-adenine-dinucleotide-nadh-by-incorporation-of-neutral-red-in-aluminum-doped-nanostructured-zno-thin-films
#9
Fidal V T, Chandra T S
Biosensing of NADH on bare electrodes has drawbacks such as high over-potential and poisoning during the oxidation reaction. To overcome this challenge a different approach has been undertaken by incorporating neutral red (NR) in Al doped ZnO (AZO) thin films using one-pot chemical bath deposition (CBD). The surface morphology of the films was hexagonal nanorods along the c-axis, perpendicular to the substrate. The thickness of the thin films were ranging from 400 to 3000nm varying dependent on time of deposition (30 to 150min)...
January 4, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27986658/kv%C3%AE-1-1-senses-pyridine-nucleotide-changes-in-the-mouse-heart-and-modulates-cardiac-electrical-activity
#10
Jared Tur, Kalyan C Chapalamadugu, Chris Katnik, Javier Cuevas, Aruni Bhatnagar, Srinivas M Tipparaju
The present study investigates the physiological role of Kvβ1 subunit for sensing pyridine nucleotide (NADH/NAD+) changes in the heart. We utilized Kvβ1.1 knockout or wild type mice and established that Kvβ1.1 preferentially binds with Kv4.2 and senses the pyridine nucleotide changes in the heart. The cellular action potential duration (APD) obtained from wild type cardiomyocytes showed longer APD's with lactate perfusion which increases intracellular NADH levels, while the APD's remained unaltered in the Kvβ1...
December 16, 2016: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/27979136/simultaneous-quantitation-of-nicotinamide-riboside-nicotinamide-mononucleotide-and-nicotinamide-adenine-dinucleotide-in-milk-by-a-novel-enzyme-coupled-assay
#11
Simone Ummarino, Massimo Mozzon, Federica Zamporlini, Adolfo Amici, Francesca Mazzola, Giuseppe Orsomando, Silverio Ruggieri, Nadia Raffaelli
Nicotinamide riboside, the most recently discovered form of vitamin B3, and its phosphorylated form nicotinamide mononucleotide, have been shown to be potent supplements boosting intracellular nicotinamide adenine dinucleotide (NAD) levels, thus preventing or ameliorating metabolic and mitochondrial diseases in mouse models. Here we report for the first time on the simultaneous quantitation of nicotinamide riboside, nicotinamide mononucleotide and NAD in milk by means of a fluorometric, enzyme-coupled assay...
April 15, 2017: Food Chemistry
https://www.readbyqxmd.com/read/27909649/in-silico-profiling-of-cell-growth-and-succinate-production-in-escherichia-coli-nzn111
#12
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
#13
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
#14
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/27883243/alternative-mechanistic-strategy-for-enzyme-catalysis-in-a-ni-dependent-lactate-racemase-lara-intermediate-destabilization-by-the-cofactor
#15
Xiaoyong Zhang, Lung W 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 the 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
#16
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
#17
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
#18
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
#19
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
#20
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
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