scholarly journals Reduced Nicotinamide Adenine Dinucleotide Phosphate, a Pentose Phosphate Pathway Product, Might Be a Novel Drug Candidate for Ischemic Stroke

Stroke ◽  
2016 ◽  
Vol 47 (1) ◽  
pp. 187-195 ◽  
Author(s):  
Mei Li ◽  
Zhi-Peng Zhou ◽  
Meiling Sun ◽  
Lijuan Cao ◽  
Jieyu Chen ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Pentose Phosphate Pathway ◽  
Nicotinamide Adenine Dinucleotide ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Pentose Phosphate ◽  
Nicotinamide Adenine ◽  
Drug Candidate ◽  
Reduced Nicotinamide Adenine Dinucleotide ◽  
Novel Drug

scholarly journals Theoretical Analysis of the Built-in Metabolic Pathway Effect on the Metabolism of Erythrocyte-Bioreactors That Neutralize Ammonium

Metabolites ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 36
Author(s):  
Evgeniy Protasov ◽  
Larisa Koleva ◽  
Elizaveta Bovt ◽  
Fazoil I. Ataullakhanov ◽  
Elena Sinauridze
Keyword(s):  
Steady State ◽  
Glutamate Dehydrogenase ◽  
Pentose Phosphate Pathway ◽  
Nicotinamide Adenine Dinucleotide ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Pentose Phosphate ◽  
Nicotinamide Adenine ◽  
Limiting Factor ◽  
Glutamate Dehydrogenase Activity ◽  
Reduced Nicotinamide Adenine Dinucleotide

The limitations of the efficiency of ammonium-neutralizing erythrocyte-bioreactors based on glutamate dehydrogenase and alanine aminotransferase reactions were analyzed using a mathematical model. At low pyruvate concentrations in the external medium (below about 0.3 mM), the main limiting factor is the rate of pyruvate influx into the erythrocyte from the outside, and at higher concentrations, it is the disappearance of a steady state in glycolysis if the rate of ammonium processing is higher than the critical value (about 12 mM/h). This rate corresponds to different values of glutamate dehydrogenase activity at different concentrations of pyruvate in plasma. Oxidation of reduced nicotinamide adenine dinucleotide phosphate (NADPH) by glutamate dehydrogenase decreases the fraction of NADPH in the constant pool of nicotinamide adenine dinucleotide phosphates (NADP + NADPH). This, in turn, activates the pentose phosphate pathway, where NADP reduces to NADPH. Due to the increase in flux through the pentose phosphate pathway, stabilization of the ATP concentration becomes impossible; its value increases until almost the entire pool of adenylates transforms into the ATP form. As the pool of adenylates is constant, the ADP concentration decreases dramatically. This slows the pyruvate kinase reaction, leading to the disappearance of the steady state in glycolysis.

scholarly journals The Role of Nonglycolytic Glucose Metabolism in Myocardial Recovery Upon Mechanical Unloading and Circulatory Support in Chronic Heart Failure

Circulation ◽  
2020 ◽  
Vol 142 (3) ◽  
pp. 259-274 ◽  
Author(s):  
Rachit Badolia ◽  
Dinesh K.A. Ramadurai ◽  
E. Dale Abel ◽  
Peter Ferrin ◽  
Iosif Taleb ◽  
...  
Keyword(s):  
Heart Failure ◽  
Pentose Phosphate Pathway ◽  
Carbon Metabolism ◽  
Nicotinamide Adenine Dinucleotide ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Left Ventricular ◽  
Pentose Phosphate ◽  
Myocardial Recovery ◽  
Mechanical Unloading ◽  
Reduced Nicotinamide Adenine Dinucleotide

Background: Significant improvements in myocardial structure and function have been reported in some patients with advanced heart failure (termed responders [R]) following left ventricular assist device (LVAD)–induced mechanical unloading. This therapeutic strategy may alter myocardial energy metabolism in a manner that reverses the deleterious metabolic adaptations of the failing heart. Specifically, our previous work demonstrated a post-LVAD dissociation of glycolysis and oxidative-phosphorylation characterized by induction of glycolysis without subsequent increase in pyruvate oxidation through the tricarboxylic acid cycle. The underlying mechanisms responsible for this dissociation are not well understood. We hypothesized that the accumulated glycolytic intermediates are channeled into cardioprotective and repair pathways, such as the pentose-phosphate pathway and 1-carbon metabolism, which may mediate myocardial recovery in R. Methods: We prospectively obtained paired left ventricular apical myocardial tissue from nonfailing donor hearts as well as R and nonresponders at LVAD implantation (pre-LVAD) and transplantation (post-LVAD). We conducted protein expression and metabolite profiling and evaluated mitochondrial structure using electron microscopy. Results: Western blot analysis shows significant increase in rate-limiting enzymes of pentose-phosphate pathway and 1-carbon metabolism in post-LVAD R (post-R) as compared with post-LVAD nonresponders (post-NR). The metabolite levels of these enzyme substrates, such as sedoheptulose-6-phosphate (pentose phosphate pathway) and serine and glycine (1-carbon metabolism) were also decreased in Post-R. Furthermore, post-R had significantly higher reduced nicotinamide adenine dinucleotide phosphate levels, reduced reactive oxygen species levels, improved mitochondrial density, and enhanced glycosylation of the extracellular matrix protein, α-dystroglycan, all consistent with enhanced pentose-phosphate pathway and 1-carbon metabolism that correlated with the observed myocardial recovery. Conclusions: The recovering heart appears to direct glycolytic metabolites into pentose-phosphate pathway and 1-carbon metabolism, which could contribute to cardioprotection by generating reduced nicotinamide adenine dinucleotide phosphate to enhance biosynthesis and by reducing oxidative stress. These findings provide further insights into mechanisms responsible for the beneficial effect of glycolysis induction during the recovery of failing human hearts after mechanical unloading.

scholarly journals Catalysis of pentose phosphate pathway reactions by cytoplasmic fractions from muscle, uterus and liver of the rat, and the presence of a reduced nicotinamide–adenine dinucleotide phosphate–triose phosphate oxidoreductase in rat muscle

1974 ◽  
Vol 138 (1) ◽  
pp. 71-76 ◽  
Author(s):  
Terry Wood
Keyword(s):  
Pentose Phosphate Pathway ◽  
Nicotinamide Adenine Dinucleotide ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Pentose Phosphate ◽  
Hexose Monophosphate ◽  
Triose Phosphate ◽  
Phosphogluconate Dehydrogenase ◽  
Rat Muscle ◽  
Reduced Nicotinamide Adenine Dinucleotide ◽  
Glucose 6 Phosphate Dehydrogenase

1. The enzymes of the pentose phosphate pathway were assayed in supernatant fractions from rat muscle, liver and uterus. 2. On incubation of ribose 5-phosphate with uterus and liver supernatants, triose phosphate, sedoheptulose 7-phosphate and hexose monophosphate accumulated. 3. When a muscle supernatant was used, glycerol 3-phosphate instead of triose phosphate appeared and there was a negligible accumulation of hexose monophosphate. 4. Hexose monophosphate production from ribose 5-phosphate was also followed by measuring NADP+ reduction in the presence of an excess of phosphoglucose isomerase, glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase. 5. With a muscle supernatant, NADPH was reoxidized as rapidly as it was formed owing to the presence of a NADPH–triose phosphate oxidoreductase. 6. A modification of the pentose phosphate pathway in skeletal muscle incorporating this enzyme is proposed.

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