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NAD AND nicotinamide riboside

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https://www.readbyqxmd.com/read/29782205/nad-repletion-produces-no-therapeutic-effect-in-mice-with-respiratory-chain-complex-iii-deficiency-and-chronic-energy-deprivation
#1
Janne Purhonen, Jayasimman Rajendran, Saara Tegelberg, Olli-Pekka Smolander, Eija Pirinen, Jukka Kallijärvi, Vineta Fellman
Biosynthetic precursors of NAD+ can replenish a decreased cellular NAD+ pool and, supposedly via sirtuin (SIRT) deacetylases, improve mitochondrial function. We found decreased hepatic NAD+ concentration and downregulated biosynthesis in Bcs1lp.S78G knock-in mice with respiratory chain complex III deficiency and mitochondrial hepatopathy. Aiming at ameliorating disease progression via NAD+ repletion and improved mitochondrial function, we fed these mice nicotinamide riboside (NR), a NAD+ precursor. A targeted metabolomics verified successful administration and suggested enhanced NAD+ biosynthesis in the treated mice, although hepatic NAD+ concentration was unchanged at the end point...
May 21, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29744033/nad-biosynthesis-aging-and-disease
#2
REVIEW
Sean Johnson, Shin-Ichiro Imai
Nicotinamide adenine dinucleotide (NAD + ) biosynthesis and its regulation have recently been attracting markedly increasing interest. Aging is marked by a systemic decrease in NAD + across multiple tissues. The dysfunction of NAD + biosynthesis plays a critical role in the pathophysiologies of multiple diseases, including age-associated metabolic disorders, neurodegenerative diseases, and mental disorders. As downstream effectors, NAD + -dependent enzymes, such as sirtuins, are involved in the progression of such disorders...
2018: F1000Research
https://www.readbyqxmd.com/read/29714801/chemo-enzymatic-synthesis-of-isotopically-labeled-nicotinamide-riboside
#3
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/29685734/quantitative-analysis-of-nad-synthesis-breakdown-fluxes
#4
Ling Liu, Xiaoyang Su, William J Quinn, Sheng Hui, Kristin Krukenberg, David W Frederick, Philip Redpath, Le Zhan, Karthikeyani Chellappa, Eileen White, Marie Migaud, Timothy J Mitchison, Joseph A Baur, Joshua D Rabinowitz
The redox cofactor nicotinamide adenine dinucleotide (NAD) plays a central role in metabolism and is a substrate for signaling enzymes including poly-ADP-ribose-polymerases (PARPs) and sirtuins. NAD concentration falls during aging, which has triggered intense interest in strategies to boost NAD levels. A limitation in understanding NAD metabolism has been reliance on concentration measurements. Here, we present isotope-tracer methods for NAD flux quantitation. In cell lines, NAD was made from nicotinamide and consumed largely by PARPs and sirtuins...
April 20, 2018: Cell Metabolism
https://www.readbyqxmd.com/read/29679894/nicotinamide-riboside-attenuates-alcohol-induced-liver-injuries-via-activation-of-sirt1-pgc-1%C3%AE-mitochondrial-biosynthesis-pathway
#5
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
#6
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
#7
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
#8
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/29424941/simultaneous-measurement-of-nad-metabolome-in-aged-mice-tissue-using-liquid-chromatography-tandem-mass-spectrometry
#9
Keisuke Yaku, Keisuke Okabe, Takashi Nakagawa
Nicotinamide adenine dinucleotide (NAD) is a major co-factor that mediates multiple biological processes including redox reaction and gene expression. Recently, NAD metabolism has received considerable attention because administration of NAD precursors exhibited beneficial effects against aging-related metabolic disorders in animals. Although numerous studies have reported that NAD levels decline with aging in multiple animal tissues, the pathway and kinetics of NAD metabolism in aged organs are not completely understood...
February 9, 2018: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/29413178/regulatory-effects-of-nad-metabolic-pathways-on-sirtuin-activity
#10
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
#11
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
#12
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/29317476/poly-adp-ribose-polymerase-inhibitor-pj34-attenuated-hepatic-triglyceride-accumulation-in-alcoholic-fatty-liver-disease-in-mice
#13
Shishun Huang, Bing Zhang, Yingli Chen, Huan Liu, Yang Liu, Xin Li, Zhiwei Bao, Zhenyuan Song, Zhigang Wang
Poly(ADP-ribose) polymerase (PARP) is an NAD-consuming enzyme and its specific role in the pathogenesis of alcoholic fatty liver disease (AFLD) remains elusive. In this study, we applied PJ34 [ N -(5,6-dihydro-6-oxo-2-phenanthridinyl)-2-acetamide hydrochloride] to inhibit hepatic PARP activity to examine the corresponding pathologic alteration in AFLD in mice and the underlying molecular mechanism. We found that PJ34 decreased the intracellular triglyceride (TG) content in hepatocytes. Moreover, PJ34 suppressed the gene expression of diglyceride acyltransferases DGAT1 and DGAT2 and elevated intracellular NAD+ levels in hepatocytes...
March 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29275540/synthesis-of-%C3%AE-nicotinamide-riboside-using-an-efficient-two-step-methodology
#14
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
#15
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
#16
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
#17
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/29208611/perturbations-of-nad-salvage-systems-impact-mitochondrial-function-and-energy-homeostasis-in-mouse-myoblasts-and-intact-skeletal-muscle
#18
Marianne Agerholm, Morten Dall, Benjamin A H Jensen, Clara Prats, Søren Madsen, Astrid L Basse, Anne-Sofie Graae, Steve Risis, Julie Goldenbaum, Bjørn Quistorff, Steen Larsen, Sara G Vienberg, Jonas T Treebak
Nicotinamide adenine dinucleotide (NAD+ ) can be synthesized by nicotinamide phosphoribosyltransferase (NAMPT). We aimed to determine the role of NAMPT for maintaining NAD+ levels, mitochondrial function, and metabolic homeostasis in skeletal muscle cells. We generated stable Nampt knockdown (shNampt KD) C2C12 cells using a shRNA lentiviral approach. Moreover, we applied gene electrotransfer to express cre recombinase in tibialis anterior muscle of floxed Nampt mice. In shNampt KD C2C12 myoblasts, Nampt and NAD+ levels were reduced by 70% and 50%, respectively, and maximal respiratory capacity was reduced by 25%...
December 5, 2017: American Journal of Physiology. Endocrinology and Metabolism
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
#19
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/28923496/deficiency-of-the-mitochondrial-nad-kinase-causes-stress-induced-hepatic-steatosis-in-mice
#20
Kezhong Zhang, Hyunbae Kim, Zhiyao Fu, Yining Qiu, Zhao Yang, Jiemei Wang, Deqiang Zhang, Xin Tong, Lei Yin, Jing Li, Jianmei Wu, Nathan R Qi, Sander M Houten, Ren Zhang
BACKGROUND & AIMS: The mitochondrial nicotinamide adenine dinucleotide (NAD) kinase (NADK2, also called MNADK) catalyzes phosphorylation of NAD to yield NADP. Little is known about the functions of mitochondrial NADP and MNADK in liver physiology and pathology. We investigated the effects of reduced mitochondrial NADP by deleting MNADK in mice. METHODS: We generated MNADK knockout (KO) mice on a C57BL/6NTac background; mice with a wild-type Mnadk gene were used as controls...
January 2018: Gastroenterology
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