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https://www.readbyqxmd.com/read/29714801/chemo-enzymatic-synthesis-of-isotopically-labeled-nicotinamide-riboside
#1
Ai Tran, Ryota Yokose, Yana Cen
As a cofactor for numerous reactions, NAD+ is found widely dispersed across many maps of cellular metabolism. This core redox role alone makes the biosynthesis of NAD+ of great interest. Recent studies have revealed new biological roles for NAD+ as a substrate for diverse enzymes that regulate a broad spectrum of key cellular tasks. These NAD+-consuming enzymes further highlight the importance of understanding NAD+ biosynthetic pathways. In this study, we developed a chemo-enzymatic synthesis of isotopically labeled NAD+ precursor, nicotinamide riboside (NR)...
May 1, 2018: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/29679894/nicotinamide-riboside-attenuates-alcohol-induced-liver-injuries-via-activation-of-sirt1-pgc-1%C3%AE-mitochondrial-biosynthesis-pathway
#2
Sufan Wang, Ting Wan, Mingtong Ye, Yun Qiu, Lei Pei, Rui Jiang, Nengzhi Pang, Yuanling Huang, Baoxia Liang, Wenhua Ling, Xiaojun Lin, Zhenfeng Zhang, Lili Yang
BACKGROUND: Nicotinamide riboside (NR) is a nicotinamide adenine dinucleotide (NAD+ ) precursor which is present in foods such as milk and beer. It was reported that NR can prevent obesity, increase longevity, and promote liver regeneration. However, whether NR can prevent ethanol-induced liver injuries is not known. This study aimed to explore the effect of NR on ethanol induced liver injuries and the underlying mechanisms. METHODS: We fed C57BL/6 J mice with Lieber-DeCarli ethanol liquid diet with or without 400 mg/kg·bw NR for 16 days...
April 5, 2018: Redox Biology
https://www.readbyqxmd.com/read/29678570/overexpression-of-nrk1-ameliorates-diet-and-age-induced-hepatic-steatosis-and-insulin-resistance
#3
Rui Fan, Jing Cui, Feng Ren, Qingzhi Wang, Yanmei Huang, Bin Zhao, Lai Wei, Xinlai Qian, Xiwen Xiong
NAD+ is a co-enzyme in redox reactions and a substrate required for activity of various enzyme families, including sirtuins and poly(ADP-ribose) polymerases. Dietary supplementation of NAD+ precursors nicotinamide mononucleotide (NMN) or nicotinamide riboside (NR) protects against metabolic disease, neurodegenerative disorders and age-related physiological decline in mammals. Here we sought to identify the roles of nicotinamide riboside kinase 1 (NRK1) plays in regulating hepatic NAD+ biosynthesis and lipid metabolism...
June 2, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29599478/chronic-nicotinamide-riboside-supplementation-is-well-tolerated-and-elevates-nad-in-healthy-middle-aged-and-older-adults
#4
Christopher R Martens, Blair A Denman, Melissa R Mazzo, Michael L Armstrong, Nichole Reisdorph, Matthew B McQueen, Michel Chonchol, Douglas R Seals
Nicotinamide adenine dinucleotide (NAD+ ) has emerged as a critical co-substrate for enzymes involved in the beneficial effects of regular calorie restriction on healthspan. As such, the use of NAD+ precursors to augment NAD+ bioavailability has been proposed as a strategy for improving cardiovascular and other physiological functions with aging in humans. Here we provide the evidence in a 2 × 6-week randomized, double-blind, placebo-controlled, crossover clinical trial that chronic supplementation with the NAD+ precursor vitamin, nicotinamide riboside (NR), is well tolerated and effectively stimulates NAD+ metabolism in healthy middle-aged and older adults...
March 29, 2018: Nature Communications
https://www.readbyqxmd.com/read/29432159/nad-supplementation-normalizes-key-alzheimer-s-features-and-dna-damage-responses-in-a-new-ad-mouse-model-with-introduced-dna-repair-deficiency
#5
Yujun Hou, Sofie Lautrup, Stephanie Cordonnier, Yue Wang, Deborah L Croteau, Eduardo Zavala, Yongqing Zhang, Kanako Moritoh, Jennifer F O'Connell, Beverly A Baptiste, Tinna V Stevnsner, Mark P Mattson, Vilhelm A Bohr
Emerging findings suggest that compromised cellular bioenergetics and DNA repair contribute to the pathogenesis of Alzheimer's disease (AD), but their role in disease-defining pathology is unclear. We developed a DNA repair-deficient 3xTgAD/Polβ+/- mouse that exacerbates major features of human AD including phosphorylated Tau (pTau) pathologies, synaptic dysfunction, neuronal death, and cognitive impairment. Here we report that 3xTgAD/Polβ+/- mice have a reduced cerebral NAD+ /NADH ratio indicating impaired cerebral energy metabolism, which is normalized by nicotinamide riboside (NR) treatment...
February 20, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29413178/regulatory-effects-of-nad-metabolic-pathways-on-sirtuin-activity
#6
Ning Zhang, Anthony A Sauve
NAD+ acts as a crucial regulator of cell physiology and as an integral participant in cellular metabolism. By virtue of a variety of signaling activities this central metabolite can exert profound effects on organism health status. Thus, while it serves as a well-known metabolic cofactor functioning as a redox-active substrate, it can also function as a substrate for signaling enzymes, such as sirtuins, poly (ADP-ribosyl) polymerases, mono (ADP-ribosyl) transferases, and CD38. Sirtuins function as NAD+ -dependent protein deacetylases (deacylases) and catalyze the reaction of NAD+ with acyllysine groups to remove the acyl modification from substrate proteins...
2018: Progress in Molecular Biology and Translational Science
https://www.readbyqxmd.com/read/29351465/emerging-potential-benefits-of-modulating-nad-metabolism-in-cardiovascular-disease
#7
Daniel S Matasic, Charles Brenner, Barry London
Nicotinamide adenine dinucleotide (NAD+ ) and related metabolites are central mediators of fuel oxidation and bioenergetics within cardiomyocytes. Additionally, NAD+ is required for the activity of multifunctional enzymes, including sirtuins and poly(ADP-ribose) polymerases that regulate posttranslational modifications, DNA damage responses, and Ca2+ signaling. Recent research has indicated that NAD+ participates in a multitude of processes dysregulated in cardiovascular diseases. Therefore, supplementation of NAD+ precursors, including nicotinamide riboside that boosts or repletes the NAD+ metabolome, may be cardioprotective...
April 1, 2018: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29317496/a-functional-link-between-nad-homeostasis-and-n-terminal-protein-acetylation-in-saccharomyces-cerevisiae
#8
Trevor Croft, Christol James Theoga Raj, Michelle Salemi, Brett S Phinney, Su-Ju Lin
Nicotinamide adenine dinucleotide (NAD+ ) is an essential metabolite participating in cellular redox chemistry and signaling, and the complex regulation of NAD+ metabolism is not yet fully understood. To investigate this, we established a NAD+ -intermediate specific reporter system to identify factors required for salvage of metabolically linked nicotinamide (NAM) and nicotinic acid (NA). Mutants lacking components of the NatB complex, NAT3 and MDM20, appeared as hits in this screen. NatB is an Nα -terminal acetyltransferase responsible for acetylation of the N terminus of specific Met-retained peptides...
February 23, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29275540/synthesis-of-%C3%AE-nicotinamide-riboside-using-an-efficient-two-step-methodology
#9
Ning Zhang, Anthony A Sauve
A two-step chemical method for the synthesis of β-nicotinamide riboside (NR) is described. NR has achieved wide use as an NAD+ precursor (vitamin B3) and can significantly increase central metabolite NAD+ concentrations in mammalian cells. β-NR can be prepared with an efficient two-step procedure. The synthesis is initiated via coupling of commercially available 1,2,3,5-tetra-O-acetyl-β-D-ribofuranose with ethyl nicotinate in the presence of trimethylsilyl trifluoromethanesulfonate (TMSOTf).1 H NMR showed that the product was formed with complete stereoselectivity to produce only the β-isomer in high yield (>90% versus starting sugar)...
December 24, 2017: Current Protocols in Nucleic Acid Chemistry
https://www.readbyqxmd.com/read/29249689/nad-intermediates-the-biology-and-therapeutic-potential-of-nmn-and-nr
#10
REVIEW
Jun Yoshino, Joseph A Baur, Shin-Ichiro Imai
Research on the biology of NAD+ has been gaining momentum, providing many critical insights into the pathogenesis of age-associated functional decline and diseases. In particular, two key NAD+ intermediates, nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), have been extensively studied over the past several years. Supplementing these NAD+ intermediates has shown preventive and therapeutic effects, ameliorating age-associated pathophysiologies and disease conditions. Although the pharmacokinetics and metabolic fates of NMN and NR are still under intensive investigation, these NAD+ intermediates can exhibit distinct behavior, and their fates appear to depend on the tissue distribution and expression levels of NAD+ biosynthetic enzymes, nucleotidases, and presumptive transporters for each...
March 6, 2018: Cell Metabolism
https://www.readbyqxmd.com/read/29217642/nicotinamide-riboside-preserves-cardiac-function-in-a-mouse-model-of-dilated-cardiomyopathy
#11
Nicolas Diguet, Samuel A J Trammell, Cynthia Tannous, Robin Deloux, Jérôme Piquereau, Nathalie Mougenot, Anne Gouge, Mélanie Gressette, Boris Manoury, Jocelyne Blanc, Marie Breton, Jean-François Decaux, Gareth Lavery, István Baczkó, Joffrey Zoll, Anne Garnier, Zhenlin Li, Charles Brenner, Mathias Mericskay
Background -Myocardial metabolic impairment is a major feature in chronic heart failure (HF). As the major coenzyme in fuel oxidation and oxidative phosphorylation and a substrate for enzymes signaling energy stress and oxidative stress response, NAD+ is emerging as a metabolic target in a number of diseases including HF. Little is known on mechanisms regulating homeostasis of NAD+ in the failing heart. Methods -To explore possible alterations of NAD+ homeostasis in the failing heart, we quantified expression of NAD+ biosynthetic enzymes in human failing heart and in the heart of a mouse model of dilated cardiomyopathy (DCM) triggered by SRF transcription factor depletion in the heart (SRFHKO ) or of cardiac hypertrophy triggered by transverse aorta constriction (TAC)...
December 7, 2017: Circulation
https://www.readbyqxmd.com/read/29211728/an-open-label-non-randomized-study-of-the-pharmacokinetics-of-the-nutritional-supplement-nicotinamide-riboside-nr-and-its-effects-on-blood-nad-levels-in-healthy-volunteers
#12
Sophia E Airhart, Laura M Shireman, Linda J Risler, Gail D Anderson, G A Nagana Gowda, Daniel Raftery, Rong Tian, Danny D Shen, Kevin D O'Brien
OBJECTIVES: The co-primary objectives of this study were to determine the human pharmacokinetics (PK) of oral NR and the effect of NR on whole blood nicotinamide adenine dinucleotide (NAD+) levels. BACKGROUND: Though mitochondrial dysfunction plays a critical role in the development and progression of heart failure, no mitochondria-targeted therapies have been translated into clinical practice. Recent murine studies have reported associations between imbalances in the NADH/NAD+ ratio with mitochondrial dysfunction in multiple tissues, including myocardium...
2017: PloS One
https://www.readbyqxmd.com/read/29184669/repeat-dose-nrpt-nicotinamide-riboside-and-pterostilbene-increases-nad-levels-in-humans-safely-and-sustainably-a-randomized-double-blind-placebo-controlled-study
#13
Ryan W Dellinger, Santiago Roel Santos, Mark Morris, Mal Evans, Dan Alminana, Leonard Guarente, Eric Marcotulli
NRPT is a combination of nicotinamide riboside (NR), a nicotinamide adenine dinucleotide (NAD+) precursor vitamin found in milk, and pterostilbene (PT), a polyphenol found in blueberries. Here, we report this first-in-humans clinical trial designed to assess the safety and efficacy of a repeat dose of NRPT (commercially known as Basis). NRPT was evaluated in a randomized, double-blind, and placebo-controlled study in a population of 120 healthy adults between the ages of 60 and 80 years. The study consisted of three treatment arms: placebo, recommended dose of NRPT (NRPT 1X), and double dose of NRPT (NRPT 2X)...
2017: NPJ Aging and Mechanisms of Disease
https://www.readbyqxmd.com/read/28842432/nicotinamide-riboside-a-form-of-vitamin-b-3-protects-against-excitotoxicity-induced-axonal-degeneration
#14
Pauline Vaur, Bernard Brugg, Mathias Mericskay, Zhenlin Li, Mark S Schmidt, Denis Vivien, Cyrille Orset, Etienne Jacotot, Charles Brenner, Eric Duplus
NAD+ depletion is a common phenomenon in neurodegenerative pathologies. Excitotoxicity occurs in multiple neurologic disorders and NAD+ was shown to prevent neuronal degeneration in this process through mechanisms that remained to be determined. The activity of nicotinamide riboside (NR) in neuroprotective models and the recent description of extracellular conversion of NAD+ to NR prompted us to probe the effects of NAD+ and NR in protection against excitotoxicity. Here, we show that intracortical administration of NR but not NAD+ reduces brain damage induced by NMDA injection...
December 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28752046/nicotinamide-riboside-kinases-display-redundancy-in-mediating-nicotinamide-mononucleotide-and-nicotinamide-riboside-metabolism-in-skeletal-muscle-cells
#15
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/28346814/nicotinamide-riboside-a-form-of-vitamin-b3-and-nad-precursor-relieves-the-nociceptive-and-aversive-dimensions-of-paclitaxel-induced-peripheral-neuropathy-in-female-rats
#16
Marta V Hamity, Stephanie R White, Roxanne Y Walder, Mark S Schmidt, Charles Brenner, Donna L Hammond
Injury to sensory afferents may contribute to the peripheral neuropathies that develop after administration of chemotherapeutic agents. Manipulations that increase levels of nicotinamide adenine dinucleotide (NAD) can protect against neuronal injury. This study examined whether nicotinamide riboside (NR), a third form of vitamin B3 and precursor of NAD, diminishes tactile hypersensitivity and place escape-avoidance behaviors in a rodent model of paclitaxel-induced peripheral neuropathy. Female Sprague-Dawley rats received 3 intravenous injections of 6...
May 2017: Pain
https://www.readbyqxmd.com/read/28211258/effects-of-a-wide-range-of-dietary-nicotinamide-riboside-nr-concentrations-on-metabolic-flexibility-and-white-adipose-tissue-wat-of-mice-fed-a-mildly-obesogenic-diet
#17
Wenbiao Shi, Maria A Hegeman, Dorien A M van Dartel, Jing Tang, Manuel Suarez, Hans Swarts, Bart van der Hee, Lluis Arola, Jaap Keijer
SCOPE: Metabolic flexibility is the ability to switch metabolism between carbohydrate oxidation (CHO) and fatty acid oxidation (FAO) and is a biomarker for metabolic health. The effect on metabolic health of nicotinamide riboside (NR) as an exclusive source of vitamin B3 is unknown and is examined here for a wide range of NR. DESIGN AND METHODS: Nine-week-old male C57BL/6JRcc mice received a semi-purified mildly obesogenic (40 en% fat) diet containing 0.14% L-tryptophan and either 5, 15, 30, 180, or 900 mg NR per kg diet for 15 weeks...
August 2017: Molecular Nutrition & Food Research
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
#18
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)...
June 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27924925/replicatively-senescent-human-fibroblasts-reveal-a-distinct-intracellular-metabolic-profile-with-alterations-in-nad-and-nicotinamide-metabolism
#19
Emma L James, James A E Lane, Ryan D Michalek, Edward D Karoly, E Kenneth Parkinson
Cellular senescence occurs by proliferative exhaustion (PEsen) or following multiple cellular stresses but had not previously been subject to detailed metabolomic analysis. Therefore, we compared PEsen fibroblasts with proliferating and transiently growth arrested controls using a combination of different mass spectroscopy techniques. PEsen cells showed many specific alterations in both the NAD+ de novo and salvage pathways including striking accumulations of nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR) in the amidated salvage pathway despite no increase in nicotinamide phosphoribosyl transferase or in the NR transport protein, CD73...
December 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27809334/nicotinamide-adenine-dinucleotide-biosynthesis-promotes-liver-regeneration
#20
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...
February 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
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