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

FACTORS INFLUENCING TETRAZOLE REDUCTION BY REDUCED NICOTINAMIDE–ADENINE DINUCLEOTIDE IN PIGEON-HEART MITOCHONDRIA

1967 ◽  
Vol 45 (2) ◽  
pp. 299-307 ◽  
Author(s):  
C. L. Talesara ◽  
M. C. Blanchaer
Keyword(s):  
Adenosine Triphosphate ◽  
Respiratory Chain ◽  
Nicotinamide Adenine Dinucleotide ◽  
Inorganic Phosphate ◽  
Adenosine Monophosphate ◽  
Adenosine Diphosphate ◽  
Heart Mitochondria ◽  
Nicotinamide Adenine ◽  
Tetrazolium Chloride ◽  
Reduced Nicotinamide Adenine Dinucleotide

The effect of adenosine triphosphate, adenosine diphosphate, adenosine monophosphate and inorganic phosphate on the reduction of 2-(p-iodophenyi)-3-p-nitrophenyl-5-phenyl tetrazolium chloride (INT) to its formazan by reduced nicotinamide-adenine dinucleotide (NADH) was studied in pigeon-heart mitochondria. Formazan production was followed at 540 mμ in 2.2 ml medium containing 0.4–0.5 mg mitochondrial protein, 0.22 M mannitol, 0.067 M sucrose, 0.02 M Tris–chloride, 0.02 mM EDTA, 0.5–3.0 mM INT, and 38 μM NADH at pH 7.2 and 28 °C. By means of the respiratory inhibitors Amytal, rotenone, antimycin A, and cyanide, it was shown that INT diverts electrons from the respiratory chain principally at the flavoprotein level. In contrast to its inhibitory effect on "the O2-linked oxidation of NADH, 10 mM adenosine triphosphate stimulated the reaction rate and formazan yield in the present system. Equimolar inorganic phosphate also increased the initial velocity but adenosine diphosphate and adenosine monophosphate did not. Preliminary kinetic studies suggest that NADH, but not INT, combines with the form of NADH dehydrogenase in the respiratory chain with which adenosine triphosphate reacts.

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.

Synthesis and electrochemical behavior of triazole-containing nicotinamide adenine dinucleotide analogs

2010 ◽  
Vol 88 (1) ◽  
pp. 35-41
Author(s):  
Wujun Liu ◽  
Shuhua Hou ◽  
Zongbao Kent Zhao
Keyword(s):  
Glassy Carbon ◽  
Nicotinamide Adenine Dinucleotide ◽  
Solvent System ◽  
Structural Features ◽  
Nicotinamide Adenine ◽  
Carbon Electrode ◽  
Terminal Alkyne ◽  
Cyclic Voltammetric ◽  
Two Phase ◽  
Nicotinamide Mononucleotide

The coupling of 2′,3′-di-O-acetyl nicotinamide mononucleotide with 3-butyn-1-ol in the presence of 2,4,6-triisopropylbenzenesulfonyl chloride quantitatively afforded a terminal alkyne-containing intermediate. Furthermore, copper(I)-mediated Huisgen [3 + 2] cycloaddition with a series of azido compounds in a two-phase solvent system gave eight triazole-containing nicotinamide adenine dinucleotide analogs with yields over 88%. The cyclic voltammetric behaviors of these novel analogs were investigated with a glassy carbon electrode, and structural features of these analogs on their electrochemical properties were briefly discussed.

scholarly journals Anti-Diabetic Potential of Anti-Oxidant Compounds "Riboflavin, Flavin Mononucleotide and Flavin Adenine Dinucleotide" with High Therapeutic Potency through Inhibition of α-Amylase and α-Glucosidase Enzymes at Sub-Micromolar Concentrations

2020 ◽  
Vol 5 (3) ◽  
pp. 146-161
Author(s):  
Sajjad Esmaeili ◽  
◽  
Maryam Amoushahi ◽  
Hamzeh Barati ◽  
Mohabbat Ansari ◽  
...  
Keyword(s):  
Flavin Adenine Dinucleotide ◽  
Structural Features ◽  
Flavin Mononucleotide ◽  
Oh Groups ◽  
Inhibition Concentration ◽  
Vitamin B5 ◽  
Ic50 Values ◽  
Anti Oxidant ◽  
Hydrophobic Nature ◽  
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 riboflavin (RF) and vitamin B5 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 RF and vitamin B5. Therefore, the present study was conducted to evaluate the inhibitory properties of fliavin, RF, flavin mononucleotide (FMN), flavin adenine dinucleotide (FAD) and vitamin B5 against α-Amy and α-Glu. The median inhibition concentration (IC50) values for α-Glu in the presence of RF, FMN and FAD were determined 136.7±4.8, 235.4±5.2 and 78.9±3.4, respectively. The IC50 values α-Amy in the presence of RF, FMN and FAD were determined 165.6±7.1, 253.6±5.5 and 131.2±6.3, respectively. Moreover, the Ki values of RF were calculated as 14.2±1.8 and 18.6±1.7 µM for α-Glu and α-Amy in a mixed-mode. In addition, to communicate with the active site of α-Glu and α-Amy respectively, RF presented a binding energy of -8.1 and -7.3 kcal/mol, FMN -7.1 and -6.8, and FAD -10.3 and -7.8 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: Riboflavin, hydrolyzing enzymes, enzyme inhibition, hyperglycemia Introduction

Chronic nicotinamide mononucleotide supplementation elevates blood nicotinamide adenine dinucleotide levels and alters muscle motility in healthy old men

2021 ◽  
Author(s):  
Masaki Igarashi ◽  
Masaomi Miura ◽  
Yoshiko Nakagawa-Nagahama ◽  
Keisuke Yaku ◽  
Kosuke Kashiwabara ◽  
...  
Keyword(s):  
Nicotinamide Adenine Dinucleotide ◽  
Nicotinamide Adenine ◽  
Double Blind ◽  
Oral Supplementation ◽  
Healthy Elderly ◽  
Nicotinamide Mononucleotide ◽  
Parallel Group ◽  
And Performance ◽  
Old Men ◽  
Parallel Group Trial

Abstract Preclinical studies have revealed that the elevation of nicotinamide adenine dinucleotide (NAD+) levels on administration of an NAD+ precursor, nicotinamide mononucleotide (NMN), can mitigate aging-related disorders; however, human data are sparse. Therefore, we aimed to investigate whether the chronic oral supplementation of NMN can elevate blood NAD+ levels and alter physiological dysfunctions, including muscle weakness, in healthy elderly participants. We administered 250 mg NMN per day to aged men for 6 or 12 weeks (n=21 for 6 weeks, n=10 for 12 weeks) in a placebo-controlled, randomized, double blind, parallel-group trial. Chronic supplementation with NMN was well tolerated and did not cause any significant deleterious effect. Metabolomic analysis of whole blood demonstrated that the oral supplementation of NMN significantly increased the concentrations of NAD+ and NAD+ metabolites. Moreover, NMN significantly improved muscle strength and performance, which were evaluated using the 30-second chair stand test, walking speed, and grip strength, and it showed no significant effect on body composition. Thus, our evidence indicates that chronic oral NMN supplementation can be an efficient NAD+ booster for preventing aging-related muscle dysfunctions in humans.

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.

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