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

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.

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

The Chemistry of Nicotinamide Adenine Dinucleotide (NAD) Analogues Containing C-Nucleosides Related to Nicotinamide Riboside [1]

2002 ◽  
Vol 9 (7) ◽  
pp. 733-741 ◽  
Author(s):  
Krzysztof Pankiewicz ◽  
Kyoichi Watanabe ◽  
Krystyna Lesiak-Watanabe ◽  
Barry Goldstein ◽  
Hiremagalur Jayaram
Keyword(s):  
Nicotinamide Adenine Dinucleotide ◽  
Nicotinamide Adenine ◽  
Nicotinamide Riboside

scholarly journals CBMT-30. TARGETING NICOTINAMIDE ADENINE DINUCLEOTIDE BIOSYNTHESIS IN CNS TUMORS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi39-vi39
Author(s):  
Ken Lindsay ◽  
Charles Brenner ◽  
David Hockenbery ◽  
Patrick Paddison
Keyword(s):  
Nicotinamide Adenine Dinucleotide ◽  
Transcriptional Repression ◽  
Therapeutic Index ◽  
Significant Negative Correlation ◽  
Nicotinamide Adenine ◽  
Chemical Library ◽  
Nicotinamide Riboside ◽  
Library Screen ◽  
Tumor Types ◽  
And Control

Abstract Nicotinamide adenine dinucleotide (NAD) metabolic pathways have been shown to be critical targets in many cancers, including brain tumors. However, inhibiting nicotinamide metabolism has had limited efficacy in the clinic to date due to on-target side effects. To identify new metabolic vulnerabilities in human Glioblastoma, we performed a chemical library screen using 250 inhibitors of metabolic enzymes in Glioblastoma stem-like cells (GSCs) (0131 and 0827) and control hNPC-CB660 cells. Among the screen hits, we identified FK866, an inhibitor of the NAD salvage enzyme NAMPT, as having GSC-selective cytotoxicity. Taking an advantage of an alternative NAD precursor salvage pathway, we show that cytotoxicity with inhibitors of the NAMPT salvage enzyme for neural stem cells was abrogated by media addition of nicotinamide riboside (NR), while certain glioblastoma stem-like cells (GSCs) remained exquisitely sensitive. Examining our GSC isolates, we observed that hypersensitivity correlated with low/absent expression of NMRK1, a kinase required for utilization of NR. We find that 5–20% of most tumor types (CNS, non-CNS) exhibit comparably low NMRK1 mRNA expression. In looking for associations with oncogenic drivers, we noted significant negative correlation with MYCN and MYC expression for multiple tumors. We have additional data suggesting that MYC/MYCN induces the NMRK1low state via transcriptional repression. These results suggest that NAMPT inhibitors, already in clinical trials, can be administered with NR to widen the therapeutic index for NMRK1low tumors. This combined theranostic approach could protect NMRK1-proficient normal cells without compromising treatment efficacy in NMRK1low tumor cells.

Effect of Niacin on Mitochondria of Allium Cepa Root Cells

1967 ◽  
Vol 25 ◽  
pp. 78-79
Author(s):  
M. Arif Hayat
Keyword(s):  
Nicotinamide Adenine Dinucleotide ◽  
Hydrogen Transfer ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Nicotinamide Adenine ◽  
Root Tips ◽  
Root Cells ◽  
Transfer Processes ◽  
Standard Procedures ◽  
A Cell ◽  
Critical Interest

Although it is recognized that niacin (pyridine-3-carboxylic acid), incorporated as the amide in nicotinamide adenine dinucleotide (NAD) or in nicotinamide adenine dinucleotide phosphate (NADP), is a cofactor in hydrogen transfer in numerous enzyme reactions in all organisms studied, virtually no information is available on the effect of this vitamin on a cell at the submicroscopic level. Since mitochondria act as sites for many hydrogen transfer processes, the possible response of mitochondria to niacin treatment is, therefore, of critical interest.Onion bulbs were placed on vials filled with double distilled water in the dark at 25°C. After two days the bulbs and newly developed root system were transferred to vials containing 0.1% niacin. Root tips were collected at ¼, ½, 1, 2, 4, and 8 hr. intervals after treatment. The tissues were fixed in glutaraldehyde-OsO4 as well as in 2% KMnO4 according to standard procedures. In both cases, the tissues were dehydrated in an acetone series and embedded in Reynolds' lead citrate for 3-10 minutes.

Nicotinamide Adenine Dinucleotide and the Metabolism of Ethanol and Acetaldehyde

1967 ◽  
Vol 28 (2) ◽  
pp. 213-224 ◽  
Author(s):  
E. Majchrowicz ◽  
B. L. Bercaw ◽  
W. M. Cole ◽  
D. H. Gregory
Keyword(s):  
Nicotinamide Adenine Dinucleotide ◽  
Nicotinamide Adenine
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