scholarly journals The Role of Oxidized Nicotinamide Adenine Dinucleotide in Fluoride Inhibition of Active Sodium Transport in Human Erythrocytes

1972 ◽  
Vol 60 (3) ◽  
pp. 337-350 ◽  
Author(s):  
Marshall S. Millman ◽  
Akira Omachi
Keyword(s):  
Nicotinamide Adenine Dinucleotide ◽  
Rate Coefficient ◽  
Phosphoglycerate Kinase ◽  
Lactic Dehydrogenase ◽  
Human Erythrocytes ◽  
Nicotinamide Adenine ◽  
Direct Inhibition ◽  
Reaction Sequence ◽  
Induced Changes

The rate coefficient for 22Na release from previously labeled human erythrocytes was determined in the presence of 0.1–10 mM sodium fluoride (F). The oxidized nicotinamide adenine dinucleotide (NAD+) level at the end of 2 hr of incubation in tris(hydroxymethyl)aminomethane (Tris)-Ringer medium was also measured. Both parameters decreased proportionately as F concentration was raised. Both F-induced changes were immediate and were reversed by 10 mM pyruvate. The decrease in NAD+ concentration following enolase inhibition by F is attributed to a diminished rate of formation in the reaction catalyzed by lactic dehydrogenase (LDH) with undiminished continued utilization in the reaction catalyzed by glyceraldehyde-3-phosphate dehydrogenase (GAPDH). It is postulated that the NAD+ lowering limited the GAPDH step, resulting in proportionate decreases in the rates of phosphoglycerate kinase (PGK) and Na,K-dependent adenosine triphosphatase (Na,K-ATPase), a reaction sequence thought to link glycolysis with active Na extrusion. Adding pyruvate with F increased NAD+ production at the LDH step, thus reactivating GAPDH, PGK, and Na,K-ATPase and leading to the observed restoration of 22Na release. The results suggest, therefore, that F inhibits active Na transport in intact human erythrocytes indirectly through a lowering of NAD+, although, direct inhibition of the Na,K-ATPase by F may possibly occur simultaneously.

scholarly journals Cellular and mitochondrial mechanisms of atrial fibrillation

2020 ◽  
Vol 115 (6) ◽  
Author(s):  
Fleur E. Mason ◽  
Julius Ryan D. Pronto ◽  
Khaled Alhussini ◽  
Christoph Maack ◽  
Niels Voigt
Keyword(s):  
Atrial Fibrillation ◽  
Nicotinamide Adenine Dinucleotide ◽  
Molecular Mechanisms ◽  
Treatment Options ◽  
Specific Treatment ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Nicotinamide Adenine ◽  
Mitochondrial Activity ◽  
Atp Production

AbstractThe molecular mechanisms underlying atrial fibrillation (AF), the most common form of arrhythmia, are poorly understood and therefore target-specific treatment options remain an unmet clinical need. Excitation–contraction coupling in cardiac myocytes requires high amounts of adenosine triphosphate (ATP), which is replenished by oxidative phosphorylation in mitochondria. Calcium (Ca2+) is a key regulator of mitochondrial function by stimulating the Krebs cycle, which produces nicotinamide adenine dinucleotide for ATP production at the electron transport chain and nicotinamide adenine dinucleotide phosphate for the elimination of reactive oxygen species (ROS). While it is now well established that mitochondrial dysfunction plays an important role in the pathophysiology of heart failure, this has been less investigated in atrial myocytes in AF. Considering the high prevalence of AF, investigating the role of mitochondria in this disease may guide the path towards new therapeutic targets. In this review, we discuss the importance of mitochondrial Ca2+ handling in regulating ATP production and mitochondrial ROS emission and how alterations, particularly in these aspects of mitochondrial activity, may play a role in AF. In addition to describing research advances, we highlight areas in which further studies are required to elucidate the role of mitochondria in AF.

scholarly journals Impaired nicotinamide adenine dinucleotide synthesis in pyruvate kinase- deficient human erythrocytes: a mechanism for decreased total NAD content and a possible secondary cause of hemolysis

Blood ◽  
1987 ◽  
Vol 69 (4) ◽  
pp. 999-1005
Author(s):  
CR Zerez ◽  
KR Tanaka
Keyword(s):  
Pyruvate Kinase ◽  
Nicotinamide Adenine Dinucleotide ◽  
Human Erythrocytes ◽  
Atp Depletion ◽  
Nicotinamide Adenine ◽  
Atp Formation ◽  
Atp Concentration ◽  
Nad Synthesis ◽  
Atp Generation ◽  
Reduced Nicotinamide Adenine Dinucleotide

Erythrocytes from individuals with pyruvate kinase (PK) deficiency have approximately half the total (oxidized and reduced) nicotinamide adenine dinucleotide (NAD) of normal erythrocytes. In order to elucidate the mechanism(s) for the decrease in total NAD, we examined NAD synthesis in intact erythrocytes. It is demonstrated that NAD synthesis is impaired in PK-deficient erythrocytes to a degree that is dependent on the PK activity and adenosine 5′-triphosphate (ATP) concentration of these cells. After incubation in the presence of fluoride, which simulates the characteristics of PK deficiency by inhibiting enolase, normal erythrocytes had impaired NAD synthesis and decreased ATP concentrations. Fluoride did not inhibit NAD synthesis in a hemolysate system that is not dependent on glycolysis for ATP generation. These data suggest that fluoride does not inhibit the enzymes of NAD synthesis and that impairment of NAD synthesis by fluoride is mediated by decreased ATP formation. Thus, it is concluded that impaired NAD synthesis in PK-deficient erythrocytes is caused by decreased ATP formation due to the PK deficiency. Since the rate of glycolysis is limited by the availability of NAD+, it is suggested that impaired NAD synthesis causes further ATP depletion and thereby may enhance hemolysis in PK-deficient erythrocytes.

scholarly journals The ultrastructural cytochemistry of lactic dehydrogenase, succinic dehydrogenase, dihydro-nicotinamide adenine dinucleotide diaphorase and cytochrome oxidase activities in hair cell mitochondria of the guinea pig cochlea.

1975 ◽  
Vol 23 (3) ◽  
pp. 216-234 ◽  
Author(s):  
G J Spector
Keyword(s):  
Hair Cell ◽  
Cytochrome Oxidase ◽  
Nicotinamide Adenine Dinucleotide ◽  
Succinic Dehydrogenase ◽  
Lactic Dehydrogenase ◽  
Nicotinamide Adenine ◽  
Fixation Method ◽  
Inner Mitochondrial Membrane ◽  
Tetrazolium Chloride ◽  
Outer Compartment

The use of cinnamyl nitroblue tetrazolium chloride (DS-NBT) in dehydrogenase experiments (lactic dehydrogenase, succinic dehydrogenase, nicotinamide adenine dinucleotide diaphorase) and 3,3'-diaminobenzidine tetrahydrochloride (DAB) in cytochrome oxidase experiments indicated that mitochondrial oxidoreduction reactions from nicotinamide adenine dinucleotide to cytochrome oxidase are located on the inner mitochondrial membrane in the outer compartment and the intracristate spaces. These reactions behave according to the chemiosmotic hypothesis. The cochlear hair cell mitochondria are cytochemically indistinguishable from free liver mitochondria. The heterogeneous mitochondrial staining pattern is related to the osmolarity of the incubation media, solubility of the enzymes and pH of the medium, but not to the fixation method.

scholarly journals Nicotinamide adenine dinucleotide as a photocatalyst

2019 ◽  
Vol 5 (7) ◽  
pp. eaax0501 ◽  
Author(s):  
Jinhyun Kim ◽  
Sahng Ha Lee ◽  
Florian Tieves ◽  
Caroline E. Paul ◽  
Frank Hollmann ◽  
...  
Keyword(s):  
Nicotinamide Adenine Dinucleotide ◽  
Metallic Nanoparticles ◽  
Chemical Conversion ◽  
Nicotinamide Adenine ◽  
Traditional Role ◽  
Life Span Extension ◽  
Redox Biocatalysis ◽  
Total Turnover ◽  
Prosthetic Groups

Nicotinamide adenine dinucleotide (NAD+) is a key redox compound in all living cells responsible for energy transduction, genomic integrity, life-span extension, and neuromodulation. Here, we report a new function of NAD+ as a molecular photocatalyst in addition to the biological roles. Our spectroscopic and electrochemical analyses reveal light absorption and electronic properties of two π-conjugated systems of NAD+. Furthermore, NAD+ exhibits a robust photostability under UV-Vis-NIR irradiation. We demonstrate photocatalytic redox reactions driven by NAD+, such as O2 reduction, H2O oxidation, and the formation of metallic nanoparticles. Beyond the traditional role of NAD+ as a cofactor in redox biocatalysis, NAD+ executes direct photoactivation of oxidoreductases through the reduction of enzyme prosthetic groups. Consequently, the synergetic integration of biocatalysis and photocatalysis using NAD+ enables solar-to-chemical conversion with the highest-ever-recorded turnover frequency and total turnover number of 1263.4 hour−1 and 1692.3, respectively, for light-driven biocatalytic trans-hydrogenation.

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