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NAD+ AND nicotinamide

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https://www.readbyqxmd.com/read/28812382/can-elevated-lactate-and-ldh-produce-a-false-positive-enzymatic-ethanol-result-in-live-patients-presenting-to-the-emergency-department
#1
Nicholas Nacca, Michael J Hodgman, Kirselle Lao, Matthew Elkins, Michael G Holland
BACKGROUND: There have been allegations in the courtroom that elevated serum lactic acid in trauma victims can yield a falsely elevated serum ethanol assay. Most hospitals utilize an indirect method of ethanol measurement where a serum sample is added to a mix of alcohol dehydrogenase and oxidized nicotinamide adenine dinucleotide (NAD+). This allows any ethanol in the patient's serum to be metabolized to acetaldehyde, and in the process results in the reduction of NAD + to NADH. NADH is then measured using spectrophotometry...
August 16, 2017: Clinical Toxicology
https://www.readbyqxmd.com/read/28812311/nad-replenishment-with-nicotinamide-mononucleotide-protects-blood-brain-barrier-integrity-and-attenuates-delayed-tpa-induced-haemorrhagic-transformation-after-cerebral-ischemia
#2
Chun-Chun Wei, Yuan-Yuan Kong, Xia-Hua, Guo-Qiang Li, Si-Li Zheng, Ming-He Cheng, Pei Wang, Chao-Yu Miao
BACKGROUND AND PURPOSE: Tissue plasminogen activator (tPA) is the only approved pharmacological therapy for acute brain ischemia; however, a major limitation of tPA is the haemorrhagic transformation followed by tPA treatment. Here, we determine whether nicotinamide mononucleotide (NMN), a key intermediate of nicotinamide adenine dinucleotide biosynthesis, would affect tPA-induced haemorrhagic transformation. EXPERIMENTAL APPROACH: Middle cerebral artery occlusion (MCAO) was achieved in CD1 mice by introducing a filament to the left MCA for 5 hours...
August 15, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28808418/emerging-roles-of-sirt1-in-fatty-liver-diseases
#3
REVIEW
Ren-Bo Ding, Jiaolin Bao, Chu-Xia Deng
Fatty liver diseases, which are commonly associated with high-fat/calorie diet, heavy alcohol consumption and/or other metabolic disorder causes, lead to serious medical concerns worldwide in recent years. It has been demonstrated that metabolic homeostasis disruption is most likely to be responsible for this global epidemic. Sirtuins are a group of conserved nicotinamide adenine dinucleotide (NAD(+)) dependent histone and/or protein deacetylases belonging to the silent information regulator 2 (Sir2) family...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/28807785/blocking-the-cd38-cadpr-pathway-plays-a-double-edge-role-in-lps-stimulated-microglia
#4
Yi-Min Wang, Zhi-Yong Liu, Yu-Hang Ai, Li-Na Zhang, Yu Zou, Qian-Yi Peng
Whether the CD38/ cyclic ADP-ribose (cADPR) pathway plays a protective or detrimental role in neuroinflammation remains controversial. This study aimed to determine the role of CD38 in neuroinflammation using lipopolysaccharide (LPS)-stimulated BV2 microglial cells and co-cultured Neuro-2a (N2a) cells. In monoculture experiments, BV2 cells were divided into control, CD38 interference (CD38Ri), negative control (NC), LPS, CD38Ri+LPS, NC+LPS and 8-Br-cADPR+LPS groups. In co-culture experiments, N2a cells were co-cultured with BV2 cells for 48 h...
August 11, 2017: Neuroscience
https://www.readbyqxmd.com/read/28792876/nad-deficiency-congenital-malformations-and-niacin-supplementation
#5
Hongjun Shi, Annabelle Enriquez, Melissa Rapadas, Ella M M A Martin, Roni Wang, Julie Moreau, Chai K Lim, Justin O Szot, Eddie Ip, James N Hughes, Kotaro Sugimoto, David T Humphreys, Aideen M McInerney-Leo, Paul J Leo, Ghassan J Maghzal, Jake Halliday, Janine Smith, Alison Colley, Paul R Mark, Felicity Collins, David O Sillence, David S Winlaw, Joshua W K Ho, Gilles J Guillemin, Matthew A Brown, Kazu Kikuchi, Paul Q Thomas, Roland Stocker, Eleni Giannoulatou, Gavin Chapman, Emma L Duncan, Duncan B Sparrow, Sally L Dunwoodie
BACKGROUND: Congenital malformations can be manifested as combinations of phenotypes that co-occur more often than expected by chance. In many such cases, it has proved difficult to identify a genetic cause. We sought the genetic cause of cardiac, vertebral, and renal defects, among others, in unrelated patients. METHODS: We used genomic sequencing to identify potentially pathogenic gene variants in families in which a person had multiple congenital malformations...
August 10, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28783258/high-resolution-studies-of-hydride-transfer-in-the-ferredoxin-nadp-reductase-superfamily
#6
Kelsey M Kean, Russell A Carpenter, Vittorio Pandini, Giuliana Zanetti, Andrea R Hall, Rick Faber, Alessandro Aliverti, P Andrew Karplus
Ferredoxin-NADP(+) reductase (FNR) is an FAD-containing enzyme best known for catalyzing the transfer of electrons from ferredoxin (Fd) to NADP(+) to make NADPH during photosynthesis. It is also the prototype for a broad enzyme superfamily, including the NADPH oxidases (NOXs) that all catalyze similar FAD-enabled electron transfers between NAD(P)H and one-electron carriers. Here we define further mechanistic details of the NAD(P)H This article is protected by copyright. All rights reserved. ⇌ FAD hydride-transfer step of the reaction based on spectroscopic studies and high resolution (~1...
August 7, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28772201/effective-immobilization-of-alcohol-dehydrogenase-on-carbon-nanoscaffolds-for-ethanol-biofuel-cell
#7
Yogeswaran Umasankar, Bal-Ram Adhikari, Aicheng Chen
An efficient approach for immobilizing alcohol dehydrogenase (ADH) while enhancing its electron transfer ability has been developed using poly(2-(trimethylamino)ethyl methacrylate) (MADQUAT) cationic polymer and carbon nanoscaffolds. The carbon nanoscaffolds were comprised of single-walled carbon nanotubes (SWCNTs) wrapped with reduced graphene oxide (rGO). The ADH entrapped within the MADQUAT that was present on the carbon nanoscaffolds exhibited a high electron exchange capability with the electrode through its cofactor β-nicotinamide adenine dinucleotide hydrate and β-nicotinamide adenine dinucleotide reduced disodium salt hydrate (NAD(+)/NADH) redox reaction...
July 26, 2017: Bioelectrochemistry
https://www.readbyqxmd.com/read/28766915/metabolomics-analysis-reveals-distinct-profiles-of-nonmuscle-invasive-and-muscle-invasive-bladder-cancer
#8
Divya Sahu, Yair Lotan, Bryan Wittmann, Bruce Neri, Donna E Hansel
Urothelial carcinoma is the most common form of bladder cancer, but pathway changes that occur with stage-wise progression have not been well defined. We used a metabolomics approach to identify potential metabolic pathways uniquely altered in normal urothelium, nonmuscle-invasive bladder cancer (NMIBC), and muscle-invasive bladder cancer (MIBC). We performed global metabolomic profiling using GC-mass spectrometry (MS) and LC-MS platforms to identify metabolite signatures between normal urothelium and high-grade urothelial carcinoma of different stages...
August 1, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28758645/fluorometric-gas-imaging-system-sniff-cam-using-the-extinction-of-nadh-with-an-adh-reverse-reaction-for-acetaldehyde-in-the-gas-phase
#9
Kenta Iitani, Toshiyuki Sato, Munire Naisierding, Yuuki Hayakawa, Koji Toma, Takahiro Arakawa, Kohji Mitsubayashi
A gas-imaging system (sniff-cam) that allows fluorometric visualization of a two-dimensional (2-D) distribution of gaseous acetaldehyde (AcH) was developed. It employed a reverse reaction of a nicotinamide adenine dinucleotide (NADH) dependent enzyme that led to consumption of NADH in that reaction. The system was constructed with a highly sensitive camera, an ultraviolet light emitting diode array sheet, two band pass filters and an alcohol dehydrogenase (ADH)-immobilized mesh that was used for AcH detection...
July 31, 2017: Analyst
https://www.readbyqxmd.com/read/28756945/sirt1-functions-as-a-negative-regulator-of-eukaryotic-poly-a-rna-transport
#10
Peipei Shan, Guangjian Fan, Lianhui Sun, Jinqin Liu, Weifang Wang, Chen Hu, Xiaohong Zhang, Qiwei Zhai, Xiaoyu Song, Liu Cao, Yongping Cui, Shengping Zhang, Chuangui Wang
Most eukaryotic mRNAs are polyadenylated in the nucleus, and the poly(A)-tail is required for efficient mRNA export and translation. However, mechanisms governing mRNA transport remain unclear. Here, we report that the nicotinamide adenine dinucleotide (NAD)-dependent deacetylase SIRT1 acts as an energy sensor and negatively regulates poly(A)RNA transport via deacetylating a poly(A)-binding protein, PABP1. Upon energy starvation, SIRT1 interacts with and deacetylates PABP1 and deactivates its poly(A)RNA binding, leading to nuclear accumulation of PABP1 and poly(A)RNA and thus facilitating eukaryotic cells to attenuate protein synthesis and energy consumption to adapt to energy stress...
August 7, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28756747/nampt-mediated-nad-biosynthesis-as-the-internal-timing-mechanism-in-nad-world-time-is-running-in-its-own-way
#11
Borut Poljsak
The biological age of organisms differs from the chronological age and is determined by internal aging clock(s). How cells estimate time on a scale of 24 h is relatively well-studied; however, how biological time is measured by cells, tissues, organs or organisms in longer time periods (years and decades) is largely unknown. What is clear and widely agreed upon is that the link to age and age-related diseases is not chronological, as it does not depend on a fixed passage of time. Rather, this link depends on the biological age of an individual cell, tissue, organ or organism and not on time in a strictly chronological sense...
July 29, 2017: Rejuvenation Research
https://www.readbyqxmd.com/read/28756225/identification-of-novel-resistance-mechanisms-to-nampt-inhibition-via-the-de-novo-nad-biosynthesis-pathway-and-nampt-mutation
#12
Jun Guo, Lloyd T Lam, Kenton L Longenecker, Mai H Bui, Kenneth B Idler, Keith B Glaser, Julie L Wilsbacher, Chris Tse, William N Pappano, Tzu-Hsuan Huang
Cancer cells have an unusually high requirement for the central and intermediary metabolite nicotinamide adenine dinucleotide (NAD(+)), and NAD(+) depletion ultimately results in cell death. The rate limiting step within the NAD(+) salvage pathway required for converting nicotinamide to NAD(+) is catalyzed by nicotinamide phosphoribosyltransferase (NAMPT). Targeting NAMPT has been investigated as an anti-cancer strategy, and several highly selective small molecule inhibitors have been found to potently inhibit NAMPT in cancer cells, resulting in NAD(+) depletion and cytotoxicity...
July 26, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28752046/nicotinamide-riboside-kinases-display-redundancy-in-mediating-nicotinamide-mononucleotide-and-nicotinamide-riboside-metabolism-in-skeletal-muscle-cells
#13
Rachel S Fletcher, Joanna Ratajczak, Craig L Doig, Lucy A Oakey, Rebecca Callingham, Gabriella Da Silva Xavier, Antje Garten, Yasir S Elhassan, Philip Redpath, Marie E Migaud, Andrew Philp, Charles Brenner, Carles Canto, Gareth G Lavery
OBJECTIVE: Augmenting nicotinamide adenine dinucleotide (NAD(+)) availability may protect skeletal muscle from age-related metabolic decline. Dietary supplementation of NAD(+) precursors nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR) appear efficacious in elevating muscle NAD(+). Here we sought to identify the pathways skeletal muscle cells utilize to synthesize NAD(+) from NMN and NR and provide insight into mechanisms of muscle metabolic homeostasis. METHODS: We exploited expression profiling of muscle NAD(+) biosynthetic pathways, single and double nicotinamide riboside kinase 1/2 (NRK1/2) loss-of-function mice, and pharmacological inhibition of muscle NAD(+) recycling to evaluate NMN and NR utilization...
August 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28750181/sirt-1-regulates-tgf-%C3%AE-induced-dermal-fibroblast-migration-via-modulation-of-cyr61-expression
#14
Eun-Jeong Kwon, Eun-Jung Park, Hyeran Yu, Jung-Sik Huh, Jinseok Kim, Moon-Jae Cho
SIRT1 is a NAD-dependent protein deacetylase that participates in cellular regulation. The increased migration of fibroblasts is an important phenotype in fibroblast activation. The role of SIRT1 in cell migration remains controversial as to whether SIRT1 acts as an activator or suppressor of cell migration. Therefore, we have established the role of SIRT1 in the migration of human dermal fibroblasts and explored targets of SIRT1 during dermal fibroblast migration. SIRT1 and Cyr61 were expressed in human dermal fibroblasts and the stimulation with TGF-β further induced their expression...
July 27, 2017: Connective Tissue Research
https://www.readbyqxmd.com/read/28750065/biochemical-characterization-of-a-new-nicotinamidase-from-an-unclassified-bacterium-thriving-in-a-geothermal-water-stream-microbial-mat-community
#15
Rubén Zapata-Pérez, Ana-Belén Martínez-Moñino, Antonio-Ginés García-Saura, Juana Cabanes, Hideto Takami, Álvaro Sánchez-Ferrer
Nicotinamidases are amidohydrolases that convert nicotinamide into nicotinic acid, contributing to NAD+ homeostasis in most organisms. In order to increase the number of nicotinamidases described to date, this manuscript characterizes a nicotinamidase obtained from a metagenomic library fosmid clone (JFF054_F02) obtained from a geothermal water stream microbial mat community in a Japanese epithermal mine. The enzyme showed an optimum temperature of 90°C, making it the first hyperthermophilic bacterial nicotinamidase to be characterized, since the phylogenetic analysis of this fosmid clone placed it in a clade of uncultured geothermal bacteria...
2017: PloS One
https://www.readbyqxmd.com/read/28743869/nicotinamide-mononucleotide-and-related-metabolites-induce-disease-resistance-against-fungal-phytopathogens-in-arabidopsis-and-barley
#16
Akihiro Miwa, Yuji Sawada, Daisuke Tamaoki, Masami Yokota Hirai, Makoto Kimura, Kazuhiro Sato, Takumi Nishiuchi
Nicotinamide mononucleotide (NMN), a precursor of nicotinamide adenine dinucleotide (NAD), is known to act as a functional molecule in animals, whereas its function in plants is largely unknown. In this study, we found that NMN accumulated in barley cultivars resistant to phytopathogenic fungal Fusarium species. Although NMN does not possess antifungal activity, pretreatment with NMN and related metabolites enhanced disease resistance to Fusarium graminearum in Arabidopsis leaves and flowers and in barley spikes...
July 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28736426/modulation-of-mitochondrial-membrane-potential-and-ros-generation-by-nicotinamide-in-a-manner-independent-of-sirt1-and-mitophagy
#17
Seon Beom Song, So-Young Jang, Hyun Tae Kang, Bie Wei, Un-Woo Jeoun, Gye Soon Yoon, Eun Seong Hwang
Nicotinamide (NAM) plays essential roles in physiology through facilitating NAD(+) redox homeostasis. Importantly, at high doses, it protects cells under oxidative stresses, and has shown therapeutic effectiveness in a variety of disease conditions. In our previous studies, NAM lowered reactive oxygen species (ROS) levels and extended cellular life span in primary human cells. In the treated cells, levels of NAD(+)/NADH and SIRT1 activity increased, while mitochondrial content decreased through autophagy activation...
July 31, 2017: Molecules and Cells
https://www.readbyqxmd.com/read/28733523/preclinical-efficacy-of-the-novel-competitive-nampt-inhibitor-stf-118804-in-pancreatic-cancer
#18
Jair Machado Espindola-Netto, Claudia C S Chini, Mariana Tarragó, Enfeng Wang, Shamit Dutta, Krishnendu Pal, Debabrata Mukhopadhyay, Mauro Sola-Penna, Eduardo N Chini
NAD salvage is one of the pathways used to generate NAD in mammals. Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in this pathway, uses nicotinamide (NAM) to generate nicotinamide mononucleotide (NMN). NMN is one of the main precursors of NAD synthesis in cells. Our previous study showed the importance of NAMPT in maintaining NAD levels in pancreatic ductal adenocarcinoma cells (PDAC), and that the NAMPT inhibitor FK866 decreased pancreatic cancer growth. We now tested the effect of STF-118804, a new highly specific NAMPT inhibitor, in models of pancreatic ductal adenocarcinoma...
June 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28732729/crystal-structures-of-an-atypical-aldehyde-dehydrogenase-having-bidirectional-oxidizing-and-reducing-activities
#19
Kyoungho Jung, Seung-Hye Hong, Ho-Phuong-Thuy Ngo, Thien-Hoang Ho, Yeh-Jin Ahn, Deok-Kun Oh, Lin-Woo Kang
Aldehyde dehydrogenases (ALDHs) are NAD(P)(+)-dependent oxidoreductases that catalyze the oxidation of a variety of aldehydes to their acid forms. In this study, we determined the crystal structures of ALDH from Bacillus cereus (BcALDH), alone, and in complex with NAD(+) and NADP(+). This enzyme can oxidize all-trans-retinal to all-trans-retinoic acid using either NAD(+) or NADP(+) with equal efficiency, and atypically, as a minor activity, can reduce all-trans-retinal to all-trans-retinol using NADPH. BcALDH accommodated the additional 2'-phosphate of NADP(+) by expanding the cofactor-binding pocket and upshifting the AMP moiety in NADP(+)...
July 18, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28731346/kinetics-of-light-induced-intramolecular-energy-transfer-in-different-conformational-states-of-nadh
#20
Zsuzsanna Heiner, Thomas Roland, Jérémie Léonard, Stefan Haacke, Géza I Groma
When bound to a protein, the coenzyme NAD+/NADH typically exists in an extended conformation, while in aqueous solutions it can be characterized by an equilibrium of folded and unfolded structures. It was recognized long ago that in the folded conformation light absorption at the adenine ring initiates an effective energy transfer (ET) towards the nicotinamide group, but the mechanism of this process is still unexplored. Here we apply ultrafast transient absorption measurements on NADH combined with compartmental model analysis for following the kinetics of the ET...
July 21, 2017: Journal of Physical Chemistry. B
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