scholarly journals Increased nicotinamide adenine dinucleotide content and synthesis in Plasmodium falciparum-infected human erythrocytes

Blood ◽  
1990 ◽  
Vol 75 (8) ◽  
pp. 1705-1710 ◽  
Author(s):  
CR Zerez ◽  
EF Jr Roth ◽  
S Schulman ◽  
KR Tanaka
Keyword(s):  
Plasmodium Falciparum ◽  
Nicotinic Acid ◽  
Nicotinamide Adenine Dinucleotide ◽  
Biosynthetic Pathway ◽  
Pentose Phosphate ◽  
Nicotinamide Adenine ◽  
Nicotinamide Phosphoribosyltransferase ◽  
Nad Synthesis ◽  
Infected Rbcs ◽  
Nicotinic Acid Phosphoribosyltransferase

Plasmodium falciparum-infected red blood cells (RBCs) are characterized by increases in the activity of glycolytic enzymes. Because nicotinamide adenine dinucleotide (NAD) and NAD phosphate (NADP) are cofactors in the reactions of glycolysis and pentose phosphate shunt, we have examined NAD and NADP content in P. falciparum-infected RBCs. Although NADP content was not significantly altered, NAD content was increased approximately 10-fold in infected RBCs (66% parasitemia) compared with uninfected control RBCs. To determine the mechanism for the increase in NAD content, we examined the activity of several NAD biosynthetic enzymes. It is known that normal human RBCs make NAD exclusively from nicotinic acid and lack the capacity to make NAD from nicotinamide. We demonstrate that infected RBCs have readily detectable nicotinamide phosphoribosyltransferase (NPRT), the first enzyme in the NAD biosynthetic pathway that uses nicotinamide, and abundant nicotinamide deamidase, the enzyme that converts nicotinamide to nicotinic acid, thereby indicating that infected RBCs can make NAD from nicotinamide. In addition, infected RBCs have a threefold increase in nicotinic acid phosphoribosyltransferase (NAPRT), the first enzyme in the NAD biosynthetic pathway that uses nicotinic acid. Thus, the increase in NAD content in P falciparum-infected RBCs appears to be mediated by increases in NAD synthesis from both nicotinic acid and nicotinamide.

scholarly journals Increased nicotinamide adenine dinucleotide content and synthesis in Plasmodium falciparum-infected human erythrocytes

Blood ◽  
1990 ◽  
Vol 75 (8) ◽  
pp. 1705-1710 ◽  
Author(s):  
CR Zerez ◽  
EF Jr Roth ◽  
S Schulman ◽  
KR Tanaka
Keyword(s):  
Plasmodium Falciparum ◽  
Nicotinic Acid ◽  
Nicotinamide Adenine Dinucleotide ◽  
Biosynthetic Pathway ◽  
Pentose Phosphate ◽  
Nicotinamide Adenine ◽  
Nicotinamide Phosphoribosyltransferase ◽  
Nad Synthesis ◽  
Infected Rbcs ◽  
Nicotinic Acid Phosphoribosyltransferase

Abstract Plasmodium falciparum-infected red blood cells (RBCs) are characterized by increases in the activity of glycolytic enzymes. Because nicotinamide adenine dinucleotide (NAD) and NAD phosphate (NADP) are cofactors in the reactions of glycolysis and pentose phosphate shunt, we have examined NAD and NADP content in P. falciparum-infected RBCs. Although NADP content was not significantly altered, NAD content was increased approximately 10-fold in infected RBCs (66% parasitemia) compared with uninfected control RBCs. To determine the mechanism for the increase in NAD content, we examined the activity of several NAD biosynthetic enzymes. It is known that normal human RBCs make NAD exclusively from nicotinic acid and lack the capacity to make NAD from nicotinamide. We demonstrate that infected RBCs have readily detectable nicotinamide phosphoribosyltransferase (NPRT), the first enzyme in the NAD biosynthetic pathway that uses nicotinamide, and abundant nicotinamide deamidase, the enzyme that converts nicotinamide to nicotinic acid, thereby indicating that infected RBCs can make NAD from nicotinamide. In addition, infected RBCs have a threefold increase in nicotinic acid phosphoribosyltransferase (NAPRT), the first enzyme in the NAD biosynthetic pathway that uses nicotinic acid. Thus, the increase in NAD content in P falciparum-infected RBCs appears to be mediated by increases in NAD synthesis from both nicotinic acid and nicotinamide.

COMPARISON OF NICOTINAMIDE ADENINE DINUCLEOTIDE SYNTHESIS BY MYCOBACTERIUM TUBERCULOSIS AND MYCOBACTERIUM BOVIS

1966 ◽  
Vol 12 (6) ◽  
pp. 1225-1233
Author(s):  
Mary A. Dudley ◽  
Hilda Pope Willett
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Nicotinic Acid ◽  
Mycobacterium Bovis ◽  
Nicotinamide Adenine Dinucleotide ◽  
Enzymatic Reaction ◽  
Nicotinamide Adenine ◽  
Nad Synthesis ◽  
Acid Accumulation

The R1Rv strain of M. tuberculosis utilized nicotinic acid for the synthesis of nicotinamide adenine dinucleotide (NAD). Nicotinic acid mononucleotide (NaMN) and nicotinic acid dinucleotide (NaAD) were identified among the enzymatic reaction mixture products. A comparison with M. bovis demonstrated a greater capacity for NAD synthesis by the bovine bacillus. It has been hypothesized that reduced NAD synthesis and failure to utilize intermediates which continue to be produced are responsible for the excessive nicotinic acid accumulation by M. tuberculosis.

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 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 Nicotinate, quinolinate and nicotinamide as precursors in the biosynthesis of nicotinamide–adenine dinucleotide in barley

1969 ◽  
Vol 115 (4) ◽  
pp. 679-685 ◽  
Author(s):  
I. J. Ryrie ◽  
K. J. Scott
Keyword(s):  
Nicotinic Acid ◽  
Nicotinamide Adenine Dinucleotide ◽  
Erysiphe Graminis ◽  
Nicotinamide Adenine ◽  
Nad Biosynthesis ◽  
Barley Leaves

1. The relative efficiencies of nicotinate, quinolinate and nicotinamide as precursors of NAD+ were measured in the first leaf of barley seedlings. 2. In small amounts, both [14C]nicotinate and [14C]quinolinate were quickly and efficiently incorporated into NAD+ and some evidence is presented suggesting that NAD+ is formed from each via nicotinic acid mononucleotide and deamido-NAD. 3. [14C]Nicotinamide served equally well as a precursor of NAD+ and although significant amounts of [14C]NMN were detected, most of the [14C]NAD+ was derived from nicotinate intermediates formed by deamination of [14C]nicotinamide. 4. Radioactive NMN was also a product of the metabolism of [14C]nicotinate and [14C]quinolinate but most probably it arose from the breakdown of [14C]NAD+. 5. In barley leaves where the concentration of NAD+ is markedly increased by infection with Erysiphe graminis, the pathways of NAD+ biosynthesis did not appear to be altered after infection. A comparison of the rates of [14C]NAD+ formation in infected and non-infected leaves indicated that the increase in NAD+ content was not due to an increased rate of synthesis.

scholarly journals IL8 Drives an Elaborate Signal Transduction Process for CD38 to Produce NAADP from NAAD and NADP+ in Endolysosomes to Effect Cell Migration

2020 ◽  
Author(s):  
Tae-Sik Nam ◽  
Dae-Ryoung Park ◽  
So-Young Rah ◽  
Tae-Gyu Woo ◽  
Hun Taeg Chung ◽  
...  
Keyword(s):  
Cell Migration ◽  
Nicotinic Acid ◽  
Nicotinamide Adenine Dinucleotide ◽  
Connexin 43 ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Nicotinamide Adenine ◽  
Type Ii ◽  
Lymphokine Activated Killer Cells ◽  
Base Exchange

AbstractNicotinic acid adenine dinucleotide phosphate (NAADP) is an obligate driver of calcium signaling whose formation from other metabolites of nicotinamide adenine dinucleotide (NAD+) has remained elusive. In vitro, CD38-mediated NAADP synthesis requires an acidic pH and a nonphysiological concentration of nicotinic acid (NA). We discovered that the type II membrane form of CD38 catalyzes synthesis of NAADP by exchanging the nicotinamide moiety of nicotinamide adenine dinucleotide phosphate (NADP+) for the NA group of nicotinic acid adenine dinucleotide (NAAD) inside endolysosomes of interleukin 8 (IL8)-treated lymphokine-activated killer cells. Upon IL8 stimulation, cytosolic NADP+ is transported to acidified endolysosomes via connexin 43 via cAMP-EPAC-RAP1-PP2A signaling. Luminal CD38 then performs a base exchange reaction with the donor NA group deriving from NAAD, produced by newly described endolysosomal activities of NA phosphoribosyltransferase and NMN adenyltransferase 3. Thus, the membrane organization of endolysosomal CD38, a signal-mediated transport system for NADP+ and luminal NAD+ biosynthetic enzymes integrate signals from a chemokine and cAMP to specify the spatiotemporal mobilization of calcium to drive cell migration.

scholarly journals NAD precursors cycle between host tissues and the gut microbiome

2021 ◽  
Author(s):  
Karthikeyani Chellappa ◽  
Melanie R McReynolds ◽  
Wenyun Lu ◽  
Xianfeng Zeng ◽  
Mikhail Makarov ◽  
...  
Keyword(s):  
Gastrointestinal Tract ◽  
Nicotinic Acid ◽  
Gut Microbiome ◽  
Nicotinamide Adenine Dinucleotide ◽  
Proximal Part ◽  
Main Route ◽  
Nicotinamide Riboside ◽  
Dietary Consumption ◽  
Nad Synthesis ◽  
Host Tissues

Nicotinamide adenine dinucleotide (NAD) is an essential redox cofactor in both mammals and microbes. Here we use isotope tracing to investigate the precursors supporting NAD synthesis in the gut microbiome. We find that preferred dietary NAD precursors are absorbed in the proximal part of the gastrointestinal tract and not available to microbes in the distal gut. Instead, circulating host nicotinamide enters the gut lumen and supports gut microbiome NAD synthesis. In addition, the microbiome converts nicotinamide, originating from the host circulation, into nicotinic acid. Host tissues uptake and utilize this microbiome-derived nicotinic acid for NAD synthesis, maintaining circulating nicotinic acid levels even in the absence of dietary consumption. Moreover, the main route from oral nicotinamide riboside, a widely used nutraceutical, to host NAD is via conversion into nicotinic acid by the gut microbiome. Thus, NAD precursors cycle between the host and gut microbiome to maintain NAD homeostasis.

scholarly journals Tryptophan plays an important role in yeast’s tolerance to isobutanol

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Hsien-Lin Liu ◽  
Christine H.-T. Wang ◽  
En-Pei Isabel Chiang ◽  
Chieh-Chen Huang ◽  
Wen-Hsiung Li
Keyword(s):  
Nicotinamide Adenine Dinucleotide ◽  
High Throughput Screening ◽  
Water Solubility ◽  
Energy Content ◽  
Enrichment Analysis ◽  
High Energy ◽  
Pentose Phosphate ◽  
Transcriptomic Analysis ◽  
Nicotinamide Adenine ◽  
Tryptophan Biosynthesis

Abstract Background Isobutanol is considered a potential biofuel, thanks to its high-energy content and octane value, limited water solubility, and compatibility with gasoline. As its biosynthesis pathway is known, a microorganism, such as Saccharomyces cerevisiae, that inherently produces isobutanol, can serve as a good engineering host. Isobutanol’s toxicity, however, is a major obstacle for bioproduction. This study is to understand how yeast tolerates isobutanol. Results A S. cerevisiae gene-deletion library with 5006 mutants was used to screen genes related to isobutanol tolerance. Image recognition was efficiently used for high-throughput screening via colony size on solid media. In enrichment analysis of the 161 isobutanol-sensitive clones identified, more genes than expected were mapped to tryptophan biosynthesis, ubiquitination, and the pentose phosphate pathway (PPP). Interestingly, adding exogenous tryptophan enabled both tryptophan biosynthesis and PPP mutant strains to overcome the stress. In transcriptomic analysis, cluster analysis of differentially expressed genes revealed the relationship between tryptophan and isobutanol stress through some specific cellular functions, such as biosynthesis and transportation of amino acids, PPP, tryptophan metabolism, nicotinate/nicotinamide metabolism (e.g., nicotinamide adenine dinucleotide biosynthesis), and fatty acid metabolism. Conclusions The importance of tryptophan in yeast’s tolerance to isobutanol was confirmed by the recovery of isobutanol tolerance in defective strains by adding exogenous tryptophan to the growth medium. Transcriptomic analysis showed that amino acid biosynthesis- and transportation-related genes in a tryptophan biosynthesis-defective host were up-regulated under conditions similar to nitrogen starvation. This may explain why ubiquitination was required for the protein turnover. PPP metabolites may serve as precursors and cofactors in tryptophan biosynthesis to enhance isobutanol tolerance. Furthermore, the tolerance mechanism may also be linked to tryptophan downstream metabolism, including the kynurenine pathway and nicotinamide adenine dinucleotide biosynthesis. Both pathways are responsible for cellular redox balance and anti-oxidative ability. Our study highlights the central role of tryptophan in yeast’s isobutanol tolerance and offers new clues for engineering a yeast host with strong isobutanol tolerance.

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.

Sign in / Sign up

Export Citation Format

Share Document