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https://www.readbyqxmd.com/read/27911769/reductive-carboxylation-is-a-major-metabolic-pathway-in-the-retinal-pigment-epithelium
#1
Jianhai Du, Aya Yanagida, Kaitlen Knight, Abbi L Engel, Anh Huan Vo, Connor Jankowski, Martin Sadilek, Van Thi Bao Tran, Megan A Manson, Aravind Ramakrishnan, James B Hurley, Jennifer R Chao
The retinal pigment epithelium (RPE) is a monolayer of pigmented cells that requires an active metabolism to maintain outer retinal homeostasis and compensate for oxidative stress. Using (13)C metabolic flux analysis in human RPE cells, we found that RPE has an exceptionally high capacity for reductive carboxylation, a metabolic pathway that has recently garnered significant interest because of its role in cancer cell survival. The capacity for reductive carboxylation in RPE exceeds that of all other cells tested, including retina, neural tissue, glial cells, and a cancer cell line...
December 1, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27909649/in-silico-profiling-of-cell-growth-and-succinate-production-in-escherichia-coli-nzn111
#2
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/27878891/cloning-and-characterization-of-the-glutamate-dehydrogenase-gene-in-streptococcus-bovis
#3
Tasuke Ando, Yoko Sugawara, Ryohei Nishio, Miho Murakami, Emiko Isogai, Hiroshi Yoneyama
Streptococcus bovis, an etiologic agent of rumen acidosis in cattle, is a rumen bacterium that can grow in a chemically defined medium containing ammonia as a sole source of nitrogen. To understand its ability to assimilate inorganic ammonia, we focused on the function of glutamate dehydrogenase. In order to identify the gene encoding this enzyme, we first amplified an internal region of the gene by using degenerate primers corresponding to hexameric family I and NAD(P)(+) binding motifs. Subsequently, inverse PCR was used to identify the whole gene, comprising an open reading frame of 1350 bp that encodes 449 amino acid residues that appear to have the substrate binding site of glutamate dehydrogenase observed in other organisms...
November 23, 2016: Animal Science Journal, Nihon Chikusan Gakkaihō
https://www.readbyqxmd.com/read/27826689/%C3%AE-hydroxybutyrate-in-the-brain-one-molecule-multiple-mechanisms
#4
Lavanya B Achanta, Caroline D Rae
β-Hydroxybutyrate (βOHB), a ketone body, is oxidised as a brain fuel. Although its contribution to energy metabolism in the healthy brain is minimal, it is an interesting metabolite which is not only oxidised but also has other direct and collateral effects which make it a molecule of interest for therapeutic purposes. In brain βOHB can be produced in astrocytes from oxidation of fatty acids or catabolism of amino acids and is metabolised in the mitochondria of all brain cell types although uptake across the blood brain barrier is a metabolic control point...
November 8, 2016: Neurochemical Research
https://www.readbyqxmd.com/read/27809334/nicotinamide-adenine-dinucleotide-biosynthesis-promotes-liver-regeneration
#5
Sarmistha Mukherjee, Karthikeyani Chellappa, Andrea Moffitt, Joan Ndungu, Ryan W Dellinger, James G Davis, Beamon Agarwal, Joseph A Baur
: The regenerative capacity of the liver is essential for recovery from surgical resection or injuries induced by trauma or toxins. During liver regeneration, the concentration of nicotinamide adenine dinucleotide (NAD) falls, at least in part due to metabolic competition for precursors. To test whether NAD availability restricts the rate of liver regeneration, we supplied nicotinamide riboside (NR), an NAD precursor, in the drinking water of mice subjected to partial hepatectomy. NR increased DNA synthesis, mitotic index, and mass restoration in the regenerating livers...
November 3, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27807756/the-yeast-scheffersomyces-amazonensis-is-an-efficient-xylitol-producer
#6
Raquel M Cadete, Monaliza A Melo-Cheab, Adriana L Viana, Evelyn S Oliveira, César Fonseca, Carlos A Rosa
This study assessed the efficiency of Scheffersomyces amazonensis UFMG-CM-Y493(T), cultured in xylose-supplemented medium (YPX) and rice hull hydrolysate (RHH), to convert xylose to xylitol under moderate and severe oxygen limitation. The highest xylitol yields of 0.75 and 1.04 g g(-1) in YPX and RHH, respectively, were obtained under severe oxygen limitation. However, volumetric productivity in RHH was ninefold decrease than that in YPX medium. The xylose reductase (XR) and xylitol dehydrogenase (XDH) activities in the YPX cultures were strictly dependent on NADPH and NAD(+) respectively, and were approximately 10% higher under severe oxygen limitation than under moderate oxygen limitation...
December 2016: World Journal of Microbiology & Biotechnology
https://www.readbyqxmd.com/read/27798266/focally-perfused-succinate-potentiates-brain-metabolism-in-head-injury-patients
#7
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/27798264/nad-repletion-improves-muscle-function-in-muscular-dystrophy-and-counters-global-parylation
#8
Dongryeol Ryu, Hongbo Zhang, Eduardo R Ropelle, Vincenzo Sorrentino, Davi A G Mázala, Laurent Mouchiroud, Philip L Marshall, Matthew D Campbell, Amir Safi Ali, Gary M Knowels, Stéphanie Bellemin, Shama R Iyer, Xu Wang, Karim Gariani, Anthony A Sauve, Carles Cantó, Kevin E Conley, Ludivine Walter, Richard M Lovering, Eva R Chin, Bernard J Jasmin, David J Marcinek, Keir J Menzies, Johan Auwerx
Neuromuscular diseases are often caused by inherited mutations that lead to progressive skeletal muscle weakness and degeneration. In diverse populations of normal healthy mice, we observed correlations between the abundance of mRNA transcripts related to mitochondrial biogenesis, the dystrophin-sarcoglycan complex, and nicotinamide adenine dinucleotide (NAD(+)) synthesis, consistent with a potential role for the essential cofactor NAD(+) in protecting muscle from metabolic and structural degeneration. Furthermore, the skeletal muscle transcriptomes of patients with Duchene's muscular dystrophy (DMD) and other muscle diseases were enriched for various poly[adenosine 5'-diphosphate (ADP)-ribose] polymerases (PARPs) and for nicotinamide N-methyltransferase (NNMT), enzymes that are major consumers of NAD(+) and are involved in pleiotropic events, including inflammation...
October 19, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27725675/nrk1-controls-nicotinamide-mononucleotide-and-nicotinamide-riboside-metabolism-in-mammalian-cells
#9
Joanna Ratajczak, Magali Joffraud, Samuel A J Trammell, Rosa Ras, Núria Canela, Marie Boutant, Sameer S Kulkarni, Marcelo Rodrigues, Philip Redpath, Marie E Migaud, Johan Auwerx, Oscar Yanes, Charles Brenner, Carles Cantó
NAD(+) is a vital redox cofactor and a substrate required for activity of various enzyme families, including sirtuins and poly(ADP-ribose) polymerases. Supplementation with NAD(+) precursors, such as nicotinamide mononucleotide (NMN) or nicotinamide riboside (NR), protects against metabolic disease, neurodegenerative disorders and age-related physiological decline in mammals. Here we show that nicotinamide riboside kinase 1 (NRK1) is necessary and rate-limiting for the use of exogenous NR and NMN for NAD(+) synthesis...
October 11, 2016: Nature Communications
https://www.readbyqxmd.com/read/27670152/hazard-identification-of-exhausts-from-gasoline-ethanol-fuel-blends-using-a-multi-cellular-human-lung-model
#10
Christoph Bisig, Michèle Roth, Loretta Müller, Pierre Comte, Norbert Heeb, Andreas Mayer, Jan Czerwinski, Alke Petri-Fink, Barbara Rothen-Rutishauser
Ethanol can be produced from biomass and as such is renewable, unlike petroleum-based fuel. Almost all gasoline cars can drive with fuel containing 10% ethanol (E10), flex-fuel cars can even use 85% ethanol (E85). Brazil and the USA already include 10-27% ethanol in their standard fuel by law. Most health effect studies on car emissions are however performed with diesel exhausts, and only few data exists for other fuels. In this work we investigated possible toxic effects of exhaust aerosols from ethanol-gasoline blends using a multi-cellular model of the human lung...
September 23, 2016: Environmental Research
https://www.readbyqxmd.com/read/27663419/inhibiting-poly-adp-ribosylation-increases-fatty-acid-oxidation-and-protects-against-fatty-liver-disease
#11
Karim Gariani, Dongryeol Ryu, Keir J Menzies, Hyon-Seung Yi, Sokrates Stein, Hongbo Zhang, Alessia Perino, Vera Lemos, Elena Katsyuba, Pooja Jha, Sandrine Vijgen, Laura Rubbia-Brandt, Yong Kyung Kim, Jung Tae Kim, Koon Soon Kim, Minho Shong, Kristina Schoonjans, Johan Auwerx
BACKGROUND & AIMS: To date, no pharmacological therapy has been approved for non-alcoholic fatty liver disease (NAFLD). The aim of the present study was to evaluate the therapeutic potential of poly ADP-ribose polymerase (PARP) inhibitors in mouse models of NAFLD. METHODS: As poly ADP-ribosylation (PARylation) of proteins by PARPs consumes nicotinamide adenine dinucleotide (NAD(+)), we hypothesized that overactivation of PARPs drives NAD(+) depletion in NAFLD. Therefore, we assessed the effectiveness of PARP inhibition to replenish NAD(+) and activate NAD(+)-dependent sirtuins, hence improving hepatic fatty acid oxidation...
September 20, 2016: Journal of Hepatology
https://www.readbyqxmd.com/read/27658974/-local-rotating-flaps-in-oculoplastic-surgery
#12
L Zikmund
AIM: In the contemporary medicine, strong emphasis is put on early closing of body surface defects, which contributes to good and early healing, but, of course, closes the entrance gate for possible infection as well. The easiest closing of the defect is the direct suture of the emerged wound. But some defects are of such an extent, so their closure is necessary to handle other way than simple suture, e.g. by rotating flap plastic surgery. In the paper are evaluated results of flap surgery technique in 56 patients...
2016: Ceská a Slovenská Oftalmologie
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
#13
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/27594836/head-to-head-comparison-of-short-term-treatment-with-the-nad-precursor-nicotinamide-mononucleotide-nmn-and-6-weeks-of-exercise-in-obese-female-mice
#14
Golam M Uddin, Neil A Youngson, David A Sinclair, Margaret J Morris
Obesity is well known to be a major cause of several chronic metabolic diseases, which can be partially counteracted by exercise. This is due, in part, to an upregulation of mitochondrial activity through increased nicotinamide adenine dinucleotide (NAD(+)). Recent studies have shown that NAD(+) levels can be increased by using the NAD(+) precursor, nicotinamide mononucleotide (NMN) leading to the suggestion that NMN could be a useful intervention in diet related metabolic disorders. In this study we compared the metabolic, and especially mitochondrial-associated, effects of exercise and NMN in ameliorating the consequences of high-fat diet (HFD) induced obesity in mice...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27567876/homocysteine-infections-polyamines-oxidative-metabolism-and-the-pathogenesis-of-dementia-and-atherosclerosis
#15
Kilmer S McCully
Hyperhomocysteinemia is a risk factor for development of dementia and Alzheimer's disease (AD), and low blood levels of folate and cobalamin are associated with hyperhomocysteinemia and AD. In elderly subjects with cognitive decline, supplementation with folate, cobalamin, and pyridoxal demonstrated reduction of cerebral atrophy in gray matter regions vulnerable to the AD process. Multiple pathogenic microbes are implicated as pathogenic factors in AD and atherosclerosis, and the deposition of amyloid-β (Aβ), phosphorylation of tau protein, neuronal injury, and apoptosis in AD are secondary to microbial infection...
October 18, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27489522/the-nad-precursor-nicotinamide-riboside-decreases-exercise-performance-in-rats
#16
Ioannis A Kourtzidis, Andreas T Stoupas, Ioannis S Gioris, Aristidis S Veskoukis, Nikos V Margaritelis, Maria Tsantarliotou, Ioannis Taitzoglou, Ioannis S Vrabas, Vassilis Paschalis, Antonios Kyparos, Michalis G Nikolaidis
BACKGROUND: Nicotinamide adenine dinucleotide (NAD(+)) and its phosphorylated form (NADP(+)) are key molecules in ubiquitous bioenergetic and cellular signaling pathways, regulating cellular metabolism and homeostasis. Thus, supplementation with NAD(+) and NADP(+) precursors emerged as a promising strategy to gain many and multifaceted health benefits. In this proof-of-concept study, we sought to investigate whether chronic nicotinamide riboside administration (an NAD(+) precursor) affects exercise performance...
2016: Journal of the International Society of Sports Nutrition
https://www.readbyqxmd.com/read/27393564/independent-amp-and-nad-signaling-regulates-c2c12-differentiation-and-metabolic-adaptation
#17
Chia George Hsu, Thomas J Burkholder
The balance of ATP production and consumption is reflected in adenosine monophosphate (AMP) and nicotinamide adenine dinucleotide (NAD) content and has been associated with phenotypic plasticity in striated muscle. Some studies have suggested that AMPK-dependent plasticity may be an indirect consequence of increased NAD synthesis and SIRT1 activity. The primary goal of this study was to assess the interaction of AMP- and NAD-dependent signaling in adaptation of C2C12 myotubes. Changes in myotube developmental and metabolic gene expression were compared following incubation with 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) and nicotinamide mononucleotide (NMN) to activate AMPK- and NAD-related signaling...
December 2016: Journal of Physiology and Biochemistry
https://www.readbyqxmd.com/read/27391898/evaluation-of-an-automated-system-for-reading-and-interpreting-disk-diffusion-antimicrobial-susceptibility-testing-of-fastidious-bacteria
#18
Evgeny A Idelevich, Karsten Becker, Janne Schmitz, Dennis Knaack, Georg Peters, Robin Köck
Results of disk diffusion antimicrobial susceptibility testing depend on individual visual reading of inhibition zone diameters. Therefore, automated reading using camera systems might represent a useful tool for standardization. In this study, the ADAGIO automated system (Bio-Rad) was evaluated for reading disk diffusion tests of fastidious bacteria. 144 clinical isolates (68 β-haemolytic streptococci, 28 Streptococcus pneumoniae, 18 viridans group streptococci, 13 Haemophilus influenzae, 7 Moraxella catarrhalis, and 10 Campylobacter jejuni) were tested on Mueller-Hinton agar supplemented with 5% defibrinated horse blood and 20 mg/L β-NAD (MH-F, Oxoid) according to EUCAST...
2016: PloS One
https://www.readbyqxmd.com/read/27370414/from-the-cover-zinc-deficiency-worsens-and-supplementation-prevents-high-fat-diet-induced-vascular-inflammation-oxidative-stress-and-pathological-remodeling
#19
Jun Chen, Shudong Wang, Manyu Luo, Zhiguo Zhang, Xiaozhen Dai, Maiying Kong, Lu Cai, Yuehui Wang, Bingyin Shi, Yi Tan
Obesity has become a common public health problem in the world and raises the risk of various cardiovascular diseases. Zinc is essential for multiple organs in terms of normal structure and function. The present study investigated the effects of high fat diet (HFD) induced obesity on the aorta in mice, and evaluated whether it can be affected by zinc deficiency or supplementation. Four-week-old male C57BL/6J mice were fed HFD with varied amounts of zinc (deficiency, adequate and supplementation) for 3 and 6 months...
September 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/27369375/activation-of-the-nrf2-signaling-pathway-in-usnic-acid-induced-toxicity-in-hepg2-cells
#20
Si Chen, Zhuhong Zhang, Tao Qing, Zhen Ren, Dianke Yu, Letha Couch, Baitang Ning, Nan Mei, Leming Shi, William H Tolleson, Lei Guo
Many usnic acid-containing dietary supplements have been marketed as weight loss agents, although severe hepatotoxicity and acute liver failure have been associated with their overuse. Our previous mechanistic studies revealed that autophagy, disturbance of calcium homeostasis, and ER stress are involved in usnic acid-induced toxicity. In this study, we investigated the role of oxidative stress and the Nrf2 signaling pathway in usnic acid-induced toxicity in HepG2 cells. We found that a 24-h treatment with usnic acid caused DNA damage and S-phase cell cycle arrest in a concentration-dependent manner...
July 1, 2016: Archives of Toxicology
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