Syntheses of Nicotinamide Riboside and Derivatives: Effective Agents for Increasing Nicotinamide Adenine Dinucleotide Concentrations in Mammalian Cells

2007 ◽  
Vol 50 (26) ◽  
pp. 6458-6461 ◽  
Author(s):  
Tianle Yang ◽  
Noel Yan-Ki Chan ◽  
Anthony A. Sauve
Keyword(s):  
Nicotinamide Adenine Dinucleotide ◽  
Mammalian Cells ◽  
Nicotinamide Adenine ◽  
Nicotinamide Riboside

scholarly journals Nicotinamide Phosphoribosyltransferase (Nampt)/Nicotinamide Adenine Dinucleotide (NAD) Axis Suppresses Atrial Fibrillation by Modulating the Calcium Handling Pathway

2020 ◽  
Vol 21 (13) ◽  
pp. 4655
Author(s):  
Duo Feng ◽  
DongZhu Xu ◽  
Nobuyuki Murakoshi ◽  
Kazuko Tajiri ◽  
Rujie Qin ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Nicotinamide Adenine Dinucleotide ◽  
Electrophysiological Study ◽  
Redox Homeostasis ◽  
Calcium Handling ◽  
Nicotinamide Adenine ◽  
Chow Diet ◽  
Nicotinamide Phosphoribosyltransferase ◽  
Nicotinamide Riboside ◽  
Normal Chow

Aging and obesity are the most prominent risk factors for onset of atrial fibrillation (AF). Nicotinamide phosphoribosyltransferase (Nampt) is the rate-limiting enzyme that catalyzes nicotinamide adenine dinucleotide (NAD) activity. Nampt and NAD are essential for maintenance of cellular redox homeostasis and modulation of cellular metabolism, and their expression levels decrease with aging and obesity. However, a role for Nampt in AF is unknown. The present study aims to test whether there is a role of Nampt/NAD axis in the pathogenesis of obesity-induced AF. Male C57BL/6J (WT) mice and heterozygous Nampt knockout (NKO) mice were fed with a normal chow diet (ND) or a high-fat diet (HFD). Electrophysiological study showed that AF inducibility was significantly increased in WT+HFD, NKO+ND, and NKO+HFD mice compared with WT+ND mice. AF duration was significantly longer in WT+HFD and NKO+ND mice and further prolonged in NKO+HFD mice compared with WT+ND mice and the calcium handling pathway was altered on molecular level. Also, treatment with nicotinamide riboside, a NAD precursor, partially restored the HFD-induced AF perpetuation. Overall, this work demonstrates that partially deletion of Nampt facilitated HFD-induced AF through increased diastolic calcium leaks. The Nampt/NAD axis may be a potent therapeutic target for AF.

scholarly journals Minireview: NAD+, a Circadian Metabolite with an Epigenetic Twist

Endocrinology ◽  
2012 ◽  
Vol 153 (1) ◽  
pp. 1-5 ◽  
Author(s):  
Paolo Sassone-Corsi
Keyword(s):  
Circadian Clock ◽  
Nicotinamide Adenine Dinucleotide ◽  
Mammalian Cells ◽  
Feedback Loop ◽  
Large Fraction ◽  
Sirtuin 1 ◽  
Nicotinamide Adenine ◽  
Dynamic Changes ◽  
Metabolic Functions ◽  
Transcriptional Feedback

Abstract A wide variety of endocrine, physiological, and metabolic functions follow daily oscillations. Most of these regulations are controlled at the level of gene expression by the circadian clock and, a remarkably coordinated transcription-translation machinery that exerts its function in virtually all mammalian cells. A large fraction of the genome is under control of the circadian clock, a regulation that is achieved through dynamic changes in chromatin states. Recent findings have demonstrated intimate connections between the circadian clock and epigenetic control. The case of nicotinamide adenine dinucleotide, which modulates the circadian activity of the deacetylase sirtuin 1, constitutes a paradigmatic example of the link between cyclic cellular metabolism and chromatin remodeling. Indeed, the clock transcriptional feedback loop is interlocked with the enzymatic loop of the nicotinamide adenine dinucleotide salvage pathway.

scholarly journals The senotherapeutic nicotinamide riboside raises platelet nicotinamide adenine dinucleotide levels but cannot prevent storage lesion

Transfusion ◽  
2019 ◽  
Vol 60 (1) ◽  
pp. 165-174 ◽  
Author(s):  
Willem Delabie ◽  
Wim Maes ◽  
Rosalie Devloo ◽  
Michelle R. Van den Hauwe ◽  
Karen Vanhoorelbeke ◽  
...  
Keyword(s):  
Nicotinamide Adenine Dinucleotide ◽  
Nicotinamide Adenine ◽  
Storage Lesion ◽  
Nicotinamide Riboside

Nicotinamide adenine dinucleotide metabolism in plants. I. Intermediates of biosynthesis in wheat leaves and the effect of benzimidazole

1970 ◽  
Vol 48 (12) ◽  
pp. 2267-2278 ◽  
Author(s):  
H. R. Godavari ◽  
E. R. Waygood
Keyword(s):  
Nicotinic Acid ◽  
Nicotinamide Adenine Dinucleotide ◽  
Triticum Aestivum L ◽  
Total Radioactivity ◽  
Significant Loss ◽  
Nicotinamide Adenine ◽  
Nad Metabolism ◽  
Nicotinamide Riboside ◽  
Nicotinamide Mononucleotide ◽  
Wheat Leaves

Leaves of wheat (Triticum aestivum L. var. Selkirk) were incubated with nicotinic acid-7-14C and nicotinamide-7-14C for varying time periods from 5 min to 12 h. Aliquots of alcoholic extracts of leaves were subjected to paper chromatography and radioautography to isolate the intermediates of the synthesis and breakdown of nicotinamide adenine dinucleotide. Nine compounds were isolated quantitatively and identified as intermediates in the pathway of NAD metabolism. All the intermediates were labeled rapidly and the rapidity of labeling became a problem in rigorously proving the sequential operation of the pathway. The results indicate that the Preiss-Handler pathway: nicotinic acid→nicotinic acid mononucleotide→nicotinic acid adenine dinucleotide→NAD operates in wheat leaves. The degradation of NAD proceeded from NAD→nicotinamide mononucleotide→nicotinamide riboside→nicotinamide. Deamidation of the nicotinamide to nicotinic acid initiated a fresh cycle of biosynthesis. The total radioactivity recovered in the intermediates indicates that no measurable amount was lost to other metabolic pathways. Nicotinamide is recovered without significant loss and recycled. The rapid appearance of labeled nicotinamide indicates a possible interconversion of nicotinic acid and nicotinamide. About 80% of the radioactivity accumulated was present in trigonelline which is considered, on the basis of other evidence, to be a non-toxic form of nicotinic acid. Benzimidazole treatment of the leaves increased the incorporation of 14C into NADP.

scholarly journals The Inhibitory Effects of Nucleosides, Nicotinamide Adenine Dinucleotide, Adenosine 5'-Triphosphate, Inosine, Nicotinamide Riboside and Nicotinamide Mononucleotide Against α-Amylase and α-Glucosidase Enzymes

2020 ◽  
Vol 5 (3) ◽  
pp. 182-198
Author(s):  
Fatemeh Ghorbania ◽  
◽  
Masoomeh Ghorbani ◽  
Arezou Ghahghaee ◽  
Keyword(s):  
Adenosine Triphosphate ◽  
Nicotinamide Adenine Dinucleotide ◽  
Adenosine Diphosphate ◽  
Structural Features ◽  
Nicotinamide Adenine ◽  
Oh Groups ◽  
Nicotinamide Riboside ◽  
Nicotinamide Mononucleotide ◽  
Ic50 Values ◽  
Hydrolyzing Enzymes

Diabetes is a group of metabolic disorders characterized by a high blood sugar level over a prolonged period of time. Inhibition of carbohydrate hydrolyzing enzymes leads to decrease in the absorption of glucose which is considered as one of the effective managements of diabetes mellitus. Vegetable, fruit, milk and fish are good sources of nucleosides and inosine (INO), nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) with versatile health benefits. The well-adapted structural features of these compounds for the inhibition/activation of enzymes include several available hydrogen bond (H-bond) acceptors and donors, flexible backbone and hydrophobic nature. The substrates of α-amylase (α-Amy) and α-Glucosidase (α-Glu), known as key absorbing enzymes, have functional groups (OH groups) resembling nucleosides. Therefore, the present study was conducted to evaluate the inhibitory properties of nucleosides against αAmy and α-Glu. The median inhibition concentration (IC50) values for α-Glu in the presence of adenosine (ADN), adenosine triphosphate (AMP), NR, INO, adenosine triphosphate (ATP), nicotinamide adenine dinucleotide (NAD), Adenosine diphosphate (ADP)-ribose, ADP-glucose and NMN were determined 208.6±3.8, 254.1±5.2, 177.7±4.8, 192.1±5.2, 215.9±2.7, 65.4±1.3, 63.4±2.2, 75.6±4.2 and 196.1±2.6, respectively. The IC50 values α-Amy in the presence of ADN, AMP, NR, INO, ATP, NAD, ADP-ribose, ADP-glucose and NMN were determined 145.3±2.4, 202.3±3.9, 127.7±4.8, 163.5±3.6, 185.3±1.2, 80.4±2.8, 64.8±4.7, 51.1±1.6 and 166.5±1.4, respectively. Moreover, the Ki values of NAD were calculated as 13.8±0.8 and 18.6±2.4 µM for α-Glu and α-Amy in a competitive-mode and noncompetitive -mode inhibition. In addition, to communicate with the active site of α-Glu and α-Amy respectively, NR presented a binding energy of -7.8 and -6.8 kcal/mol, INO -7.3 and -6.9, ATP -8.3 and -7.3, NAD -10.0 and -8.5, ADP-ribose -8.7 and -7.4, ADP-glucose -8.9 and -7.6, cAMP -6.6 and -6.3 and NMN -6.8 and -7.0 kcal/mol. These antioxidant inhibitors may be potential anti-diabetic drugs, not only to reduce glycemic index, but also to limit the activity of the major reactive oxygen species (ROS) producing pathways. Key words: Nucleosides, NAD, hydrolyzing enzymes, enzyme inhibition, hyperglycemia

scholarly journals Mammalian Nudix proteins cleave nucleotide metabolite caps on RNAs

2020 ◽  
Vol 48 (12) ◽  
pp. 6788-6798 ◽  
Author(s):  
Sunny Sharma ◽  
Ewa Grudzien-Nogalska ◽  
Keith Hamilton ◽  
Xinfu Jiao ◽  
Jun Yang ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Nicotinamide Adenine Dinucleotide ◽  
Mammalian Cells ◽  
Flavin Adenine Dinucleotide ◽  
Nicotinamide Adenine ◽  
Nudix Hydrolase ◽  
Decapping Enzymes ◽  
Hydrolysis Of ◽  
In Cells

Abstract We recently reported the presence of nicotinamide adenine dinucleotide (NAD)-capped RNAs in mammalian cells and a role for DXO and the Nudix hydrolase Nudt12 in decapping NAD-capped RNAs (deNADding) in cells. Analysis of 5′caps has revealed that in addition to NAD, mammalian RNAs also contain other metabolite caps including flavin adenine dinucleotide (FAD) and dephosphoCoA (dpCoA). In the present study we systematically screened all mammalian Nudix proteins for their potential deNADing, FAD cap decapping (deFADding) and dpCoA cap decapping (deCoAping) activity. We demonstrate that Nudt16 is a novel deNADding enzyme in mammalian cells. Additionally, we identified seven Nudix proteins—Nudt2, Nudt7, Nudt8, Nudt12, Nudt15, Nudt16 and Nudt19, to possess deCoAping activity in vitro. Moreover, our screening revealed that both mammalian Nudt2 and Nudt16 hydrolyze FAD-capped RNAs in vitro with Nudt16 regulating levels of FAD-capped RNAs in cells. All decapping activities identified hydrolyze the metabolite cap substrate within the diphosphate linkage. Crystal structure of human Nudt16 in complex with FAD at 2.7 Å resolution provide molecular insights into the binding and metal-coordinated hydrolysis of FAD by Nudt16. In summary, our study identifies novel cellular deNADding and deFADding enzymes and establishes a foundation for the selective functionality of the Nudix decapping enzymes on non-canonical metabolite caps.

scholarly journals Autofluorescence of viable cultured mammalian cells.

1979 ◽  
Vol 27 (1) ◽  
pp. 36-43 ◽  
Author(s):  
J E Aubin
Keyword(s):  
Nicotinamide Adenine Dinucleotide ◽  
Mammalian Cells ◽  
Flow System ◽  
Emission Spectra ◽  
Culture Conditions ◽  
Nicotinamide Adenine ◽  
Species Comparison ◽  
Cytoplasmic Vesicle ◽  
Intrinsic Protein ◽  
Viable Cells

The autofluorescence other than intrinsic protein emission of viable cultured mammalian cells has been investigated. The fluorescence was found to originate in discrete cytoplasmic vesicle-like regions and to be absent from the nucleus. Excitation and emission spectra of viable cells revealed at least two distinct fluorescent species. Comparison of cell spectra with spectra of known cellular metabolites suggested that most, if not all, of the fluorescence arises from intracellular nicotinamide adenine dinucleotide (NADH) and riboflavin and flavin coenzymes. Various changes in culture conditions did not affect the observed autofluorescence intensity. A multiparameter flow system (MACCS) was used to compare the fluorescence intensities of numerous cultured mammalian cells.

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