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 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.

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.

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 Microbial NAD Metabolism: Lessons from Comparative Genomics

2009 ◽  
Vol 73 (3) ◽  
pp. 529-541 ◽  
Author(s):  
Francesca Gazzaniga ◽  
Rebecca Stebbins ◽  
Sheila Z. Chang ◽  
Mark A. McPeek ◽  
Charles Brenner
Keyword(s):  
Nicotinic Acid ◽  
De Novo ◽  
Strictly Aerobic ◽  
Bacterial Dna ◽  
Nad Metabolism ◽  
Dna Ligases ◽  
Nicotinamide Riboside ◽  
Nad Synthesis ◽  
Biochemical Genetic ◽  
Lysine Deacetylases

SUMMARY NAD is a coenzyme for redox reactions and a substrate of NAD-consuming enzymes, including ADP-ribose transferases, Sir2-related protein lysine deacetylases, and bacterial DNA ligases. Microorganisms that synthesize NAD from as few as one to as many as five of the six identified biosynthetic precursors have been identified. De novo NAD synthesis from aspartate or tryptophan is neither universal nor strictly aerobic. Salvage NAD synthesis from nicotinamide, nicotinic acid, nicotinamide riboside, and nicotinic acid riboside occurs via modules of different genes. Nicotinamide salvage genes nadV and pncA, found in distinct bacteria, appear to have spread throughout the tree of life via horizontal gene transfer. Biochemical, genetic, and genomic analyses have advanced to the point at which the precursors and pathways utilized by a microorganism can be predicted. Challenges remain in dissecting regulation of pathways.

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 Nicotinamide mononucleotide (NMN) deamidation by the gut microbiome and evidence for indirect upregulation of the NAD+ metabolome

2020 ◽  
Author(s):  
Lynn-Jee Kim ◽  
Timothy J. Chalmers ◽  
Greg C. Smith ◽  
Abhirup Das ◽  
Eric Wing Keung Poon ◽  
...  
Keyword(s):  
Nicotinic Acid ◽  
Gut Microbiome ◽  
Nicotinamide Adenine Dinucleotide ◽  
Fold Increase ◽  
Health It ◽  
Isotope Labelling ◽  
Nicotinamide Mononucleotide ◽  
Age Related ◽  
Recycling Pathway ◽  
Direct Incorporation

ABSTRACTTreatment with nicotinamide mononucleotide (NMN) is a prominent strategy to address the age-related decline in nicotinamide adenine dinucleotide (NAD+) levels for maintaining aspects of late-life health. It is assumed that exogenous NMN is directly incorporated into NAD+ in mammals by the canonical recycling pathway, however the need for NAD+ is conserved across evolution, including bacteria in the gut microbiome, which can deamidate NMN to nicotinic acid mononucleotide (NaMN). Here, we use strategic isotope labelling studies to demonstrate a role for the gut microbiome in deamidating orally delivered NMN into NaMN prior to its uptake and incorporation in mammals. Microbiome depletion increased the overall abundance of NAD metabolites, suggesting a competition relationship. Strikingly, treatment with labelled NMN increased the production of unlabelled NAD precursors, with a greater than 3-fold increase in endogenous NR levels in the gut of antibiotics treated animals upon labelled NMN treatment. These data suggest that exogenous NMN impacts the NAD metabolome through indirect means, rather than through its direct incorporation, including through the production of endogenous NR via an as-yet unidentified pathway, and demonstrate an important role for the gut microbiome in the assimilation of orally delivered NMN.

scholarly journals Equilibrative Nucleoside Transporters Mediate the Import of Nicotinamide Riboside and Nicotinic Acid Riboside into Human Cells

2021 ◽  
Vol 22 (3) ◽  
pp. 1391
Author(s):  
Andrey Kropotov ◽  
Veronika Kulikova ◽  
Kirill Nerinovski ◽  
Alexander Yakimov ◽  
Maria Svetlova ◽  
...  
Keyword(s):  
Nicotinic Acid ◽  
Mammalian Cells ◽  
Experimental Models ◽  
The Body ◽  
Nucleoside Transporters ◽  
Hek293 Cells ◽  
Nucleoside Transporter ◽  
Vitamin B3 ◽  
Animal Cells ◽  
Nicotinamide Riboside

Nicotinamide riboside (NR), a new form of vitamin B3, is an effective precursor of nicotinamide adenine dinucleotide (NAD+) in human and animal cells. The introduction of NR into the body effectively increases the level of intracellular NAD+ and thereby restores physiological functions that are weakened or lost in experimental models of aging and various pathologies. Despite the active use of NR in applied biomedicine, the mechanism of its transport into mammalian cells is currently not understood. In this study, we used overexpression of proteins in HEK293 cells, and metabolite detection by NMR, to show that extracellular NR can be imported into cells by members of the equilibrative nucleoside transporter (ENT) family ENT1, ENT2, and ENT4. After being imported into cells, NR is readily metabolized resulting in Nam generation. Moreover, the same ENT-dependent mechanism can be used to import the deamidated form of NR, nicotinic acid riboside (NAR). However, NAR uptake into HEK293 cells required the stimulation of its active utilization in the cytosol such as phosphorylation by NR kinase. On the other hand, we did not detect any NR uptake mediated by the concentrative nucleoside transporters (CNT) CNT1, CNT2, or CNT3, while overexpression of CNT3, but not CNT1 or CNT2, moderately stimulated NAR utilization by HEK293 cells.

MICROBIOMA: AMIGO O ENEMIGO EN PACIENTES CON COVID - 19

SCIENTIARVM ◽  
2015 ◽  
Vol 1 (1) ◽  
pp. 15-21
Author(s):  
Katherine Milagros Quispe Medina ◽  
◽  
Angel Sixto Mamani Ruelas ◽  
Brenda Jasmin Alvarez Vera ◽  
Yasmin Yessenia Silvestre Gutierrez ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Gastrointestinal Tract ◽  
Molecular Biology ◽  
Gut Microbiome ◽  
Next Generation ◽  
Multiple Factors ◽  
Lung Microbiome ◽  
The Relationship ◽  
Generation Sequencing ◽  
Clinical Cases

The research of the microbiome concerning various diseases has grown in the last ten years due to the advances in molecular biology and next-generation sequencing, finding interactions with various pathologies. The new coronavirus 19 (SARS-COV 2) pandemic has aroused interest in the study of multiple factors that could influence in the development of symptoms mainly due to the interaction of the microbiome whether of the respiratory or gastrointestinal tract finally in the prognosis. Therefore, in this study, we focus on reviewing and analyzing the current bibliography of research and clinical cases about the relationship between the lung and gut microbiome and COVID-19, highlighting its effect on infected patients, aiming to contribute to this new line of research. Keywords: Microbiome, COVID-19, SARS-COV 2, gut microbiome, lung microbiome.

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.

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