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NAD+ AND nicotinic acid

Timothy J Brickman, Ryan J Suhadolc, Pamela J McKelvey, Sandra K Armstrong
NAD is produced via de novo biosynthesis pathways and by salvage or recycling routes. The classical Bordetella bacterial species are known to be auxotrophic for nicotinamide or nicotinic acid. This study confirmed that Bordetella bronchiseptica, Bordetella pertussis, and Bordetella parapertussis have the recycling/salvage pathway genes pncA and pncB, for use of nicotinamide or nicotinic acid, respectively, for NAD synthesis. Although these Bordetellae lack the nadA and nadB genes needed for de novo NAD biosynthesis, remarkably, they have one de novo pathway gene, nadC, encoding quinolinate phosphoribosyltransferase...
October 26, 2016: Molecular Microbiology
D L Misner, M A Kauss, J Singh, H Uppal, A Bruening-Wright, B M Liederer, T Lin, B McCray, N La, T Nguyen, D Sampath, P S Dragovich, T O'Brien, T S Zabka
Nicotinamide phosphoribosyltransferase (NAMPT) is a pleiotropic protein that functions as an enzyme, cytokine, growth factor and hormone. As a target for oncology, NAMPT is particularly attractive, because it catalyzes the rate-limiting step in the salvage pathway to generate nicotinamide adenine dinucleotide (NAD), a universal energy- and signal-carrying molecule involved in cellular energy metabolism and many homeostatic functions. Inhibition of NAMPT generally results in NAD depletion, followed by ATP reduction and loss of cell viability...
October 25, 2016: Cardiovascular Toxicology
Joanna Ratajczak, Magali Joffraud, Samuel A J Trammell, Rosa Ras, Núria Canela, Marie Boutant, Sameer S Kulkarni, Marcelo Rodrigues, Philip Redpath, Marie E Migaud, Johan Auwerx, Oscar Yanes, Charles Brenner, Carles Cantó
NAD(+) is a vital redox cofactor and a substrate required for activity of various enzyme families, including sirtuins and poly(ADP-ribose) polymerases. Supplementation with NAD(+) precursors, such as nicotinamide mononucleotide (NMN) or nicotinamide riboside (NR), protects against metabolic disease, neurodegenerative disorders and age-related physiological decline in mammals. Here we show that nicotinamide riboside kinase 1 (NRK1) is necessary and rate-limiting for the use of exogenous NR and NMN for NAD(+) synthesis...
October 11, 2016: Nature Communications
Samuel A J Trammell, Mark S Schmidt, Benjamin J Weidemann, Philip Redpath, Frank Jaksch, Ryan W Dellinger, Zhonggang Li, E Dale Abel, Marie E Migaud, Charles Brenner
Nicotinamide riboside (NR) is in wide use as an NAD(+) precursor vitamin. Here we determine the time and dose-dependent effects of NR on blood NAD(+) metabolism in humans. We report that human blood NAD(+) can rise as much as 2.7-fold with a single oral dose of NR in a pilot study of one individual, and that oral NR elevates mouse hepatic NAD(+) with distinct and superior pharmacokinetics to those of nicotinic acid and nicotinamide. We further show that single doses of 100, 300 and 1,000 mg of NR produce dose-dependent increases in the blood NAD(+) metabolome in the first clinical trial of NR pharmacokinetics in humans...
October 10, 2016: Nature Communications
Felix Schuebel, Andrea Rocker, Daniel Edelmann, Julia Schessner, Clara Brieke, Anton Meinhart
An arsenal of effector proteins is injected by bacterial pathogens into the host cell or its vicinity to increase virulence. The commonly used top-down approaches inferring the toxic mechanism of individual effector proteins from the host's phenotype are often impeded by multiple targets of different effectors as well as by their pleiotropic effects. Here we describe our bottom-up approach, showing that the bacterial type III effector AvrRxo1 of plant pathogens is an authentic phosphotransferase that produces two novel metabolites by phosphorylating nicotinamide / nicotinic acid adenine dinucleotide at the adenosine 3'-hydroxyl group...
September 12, 2016: Journal of Biological Chemistry
Laura S Kremer, Katharina Danhauser, Diran Herebian, Danijela Petkovic Ramadža, Dorota Piekutowska-Abramczuk, Annette Seibt, Wolfgang Müller-Felber, Tobias B Haack, Rafał Płoski, Klaus Lohmeier, Dominik Schneider, Dirk Klee, Dariusz Rokicki, Ertan Mayatepek, Tim M Strom, Thomas Meitinger, Thomas Klopstock, Ewa Pronicka, Johannes A Mayr, Ivo Baric, Felix Distelmaier, Holger Prokisch
To safeguard the cell from the accumulation of potentially harmful metabolic intermediates, specific repair mechanisms have evolved. APOA1BP, now renamed NAXE, encodes an epimerase essential in the cellular metabolite repair for NADHX and NADPHX. The enzyme catalyzes the epimerization of NAD(P)HX, thereby avoiding the accumulation of toxic metabolites. The clinical importance of the NAD(P)HX repair system has been unknown. Exome sequencing revealed pathogenic biallelic mutations in NAXE in children from four families with (sub-) acute-onset ataxia, cerebellar edema, spinal myelopathy, and skin lesions...
October 6, 2016: American Journal of Human Genetics
Xiaolan Wang, Beibei Liu, Yafeng Dou, Hongjie Fan, Shaohui Wang, Tao Li, Chan Ding, Shengqing Yu
UNLABELLED: Riemerella anatipestifer is a major bacterial pathogen that causes septicemic and exudative diseases in domestic ducks. In our previous study, we found that deletion of the AS87_01735 gene significantly decreased the bacterial virulence of R. anatipestifer strain Yb2 (mutant RA625). The AS87_01735 gene was predicted to encode a nicotinamidase (PncA), a key enzyme that catalyzes the conversion of nicotinamide to nicotinic acid, which is an important reaction in the NAD(+) salvage pathway...
October 1, 2016: Applied and Environmental Microbiology
Deng-Tai Wen, Lan Zheng, Liu Ni, Hui Wang, Yue Feng, Min Zhang
The CG9940 gene, which encodes the NAD(+) synthase protein in Drosophila, is conserved in human, zebra fish, and mosquito. NAD(+) synthase is a homodimer, which catalyzes the final step in de novo nicotinamide adenine dinucleotide (NAD(+)) biosynthesis, an amide transfer from either ammonia or glutamine to nicotinic acid adenine dinucleotide (NaAD). Both the CG9940 and exercise are closely relative to NAD(+) level, and NAD(+) plays important roles not only in energy metabolism and mitochondrial functions but also in aging...
October 2016: Experimental Gerontology
Yue Yang, Anthony A Sauve
We survey the historical development of scientific knowledge surrounding Vitamin B3, and describe the active metabolite forms of Vitamin B3, the pyridine dinucleotides NAD(+) and NADP(+) which are essential to cellular processes of energy metabolism, cell protection and biosynthesis. The study of NAD(+) has become reinvigorated by new understandings that dynamics within NAD(+) metabolism trigger major signaling processes coupled to effectors (sirtuins, PARPs, and CD38) that reprogram cellular metabolism using NAD(+) as an effector substrate...
December 2016: Biochimica et Biophysica Acta
Katherine A Hicks, Meigan E Yuen, Wei Feng Zhen, Tyler J Gerwig, Ryan W Story, Megan C Kopp, Mark J Snider
No abstract text is available yet for this article.
June 21, 2016: Biochemistry
Samuel Aj Trammell, Liping Yu, Philip Redpath, Marie E Migaud, Charles Brenner
BACKGROUND: Nicotinamide riboside (NR) is a recently discovered NAD(+) precursor vitamin with a unique biosynthetic pathway. Although the presence of NR in cow milk has been known for more than a decade, the concentration of NR with respect to the other NAD(+) precursors was unknown. OBJECTIVE: We aimed to determine NAD(+) precursor vitamin concentration in raw samples of milk from individual cows and from commercially available cow milk. METHODS: LC tandem mass spectrometry and isotope dilution technologies were used to quantify NAD(+) precursor vitamin concentration and to measure NR stability in raw and commercial milk...
May 2016: Journal of Nutrition
Zhu-Qing Yang, Lin-Bin Bao, Xiang-Hui Zhao, Can-Yu Wang, Shan Zhou, Lu-Hua Wen, Chuan-Bian Fu, Jian-Ming Gong, Ming-Ren Qu
Nicotinic acid (NA) acting as the precursor of NAD(+)/NADH and NADP(+)/NADPH, participates in many biochemical processes, e.g. lipid metabolism. The main purpose of this study was to investigate the effects of dietary NA on carcass traits, meat quality, blood metabolites, and fat deposition in Chinese crossbred finishing steers. Sixteen steers with the similar body weight and at the age of 24 months were randomly allocated into control group (feeding basal diet) and NA group (feeding basal diet + 1000 mg/kg NA)...
June 2016: Experimental Biology and Medicine
Hyung-Seop Youn, Tae Gyun Kim, Mun-Kyoung Kim, Gil Bu Kang, Jung Youn Kang, Jung-Gyu Lee, Jun Yop An, Kyoung Ryoung Park, Youngjin Lee, Young Jun Im, Jun Hyuck Lee, Soo Hyun Eom
Quinolinate phosphoribosyltransferase (QPRT) catalyses the production of nicotinic acid mononucleotide, a precursor of de novo biosynthesis of the ubiquitous coenzyme nicotinamide adenine dinucleotide. QPRT is also essential for maintaining the homeostasis of quinolinic acid in the brain, a possible neurotoxin causing various neurodegenerative diseases. Although QPRT has been extensively analysed, the molecular basis of the reaction catalysed by human QPRT remains unclear. Here, we present the crystal structures of hexameric human QPRT in the apo form and its complexes with reactant or product...
2016: Scientific Reports
Kerly Laskoski, Adrian R S Santos, Ana C Bonatto, Fábio O Pedrosa, Emanuel M Souza, Luciano F Huergo
Nicotinamide adenine dinucleotide synthetase enzyme (NadE) catalyzes the amination of nicotinic acid adenine dinucleotide (NaAD) to form NAD(+). This reaction represents the last step in the majority of the NAD(+) biosynthetic routes described to date. NadE enzymes typically use either glutamine or ammonium as amine nitrogen donor, and the reaction is energetically driven by ATP hydrolysis. Given the key role of NAD(+) in bacterial metabolism, NadE has attracted considerable interest as a potential target for the development of novel antibiotics...
May 2016: Archives of Microbiology
Sara Duarte-Pereira, Isabel Pereira-Castro, Sarah S Silva, Mariana Gonçalves Correia, Célia Neto, Luís Teixeira da Costa, António Amorim, Raquel M Silva
Nicotinamide adenine dinucleotide (NAD) is a cofactor in redox reactions and a substrate for NAD-consuming enzymes, such as PARPs and sirtuins. As cancer cells have increased NAD requirements, the main NAD salvage enzymes in humans, nicotinamide phosphoribosyltransferase (NAMPT) and nicotinate phosphoribosyltransferase (NAPRT), are involved in the development of novel anti-cancer therapies. Knowledge of the expression patterns of both genes in tissues and tumors is critical for the use of nicotinic acid (NA) as cytoprotective in therapies using NAMPT inhibitors...
January 12, 2016: Oncotarget
Christiane A Opitz, Ines Heiland
NAD, as well as its phosphorylated form, NADP, are best known as electron carriers and co-substrates of various redox reactions. As such they participate in approximately one quarter of all reactions listed in the reaction database KEGG. In metabolic pathway analysis, the total amount of NAD is usually assumed to be constant. That means that changes in the redox state might be considered, but concentration changes of the NAD moiety are usually neglected. However, a growing number of NAD-consuming reactions have been identified, showing that this assumption does not hold true in general...
December 2015: Biochemical Society Transactions
Katsumi Shibata
Pyridine nucleotide coenzymes (PNCs) are involved in over 500 enzyme reactions. PNCs are biosynthesized from the amino acid L-tryptophan (L-Trp), as well as the vitamin niacin. Hence, "true" niacin-deficient animals cannot be "created" using nutritional techniques. We wanted to establish a truly niacin-deficient model animal using a protocol that did not involve manipulating dietary L-Trp. We generated mice that are missing the quinolinic acid phosphoribosyltransferase (QPRT) gene. QPRT activity was not detected in qprt(-/-)mice...
2015: Journal of Nutritional Science and Vitaminology
Andrei Osterman
Universal and ubiquitous redox cofactors, nicotinamide adenine dinucleotide (NAD) and its phosphorylated analog (NADP), collectively contribute to approximately 12% of all biochemical reactions included in the metabolic model of Escherichia coli K-12. A homeostasis of the NAD pool faithfully maintained by the cells results from a dynamic balance in a network of NAD biosynthesis, utilization, decomposition, and recycling pathways that is subject to tight regulation at various levels. A brief overview of NAD utilization processes is provided in this review, including some examples of nonredox utilization...
August 2009: EcoSal Plus
Veronika Kulikova, Konstantin Shabalin, Kirill Nerinovski, Christian Dölle, Marc Niere, Alexander Yakimov, Philip Redpath, Mikhail Khodorkovskiy, Marie E Migaud, Mathias Ziegler, Andrey Nikiforov
NAD is essential for cellular metabolism and has a key role in various signaling pathways in human cells. To ensure proper control of vital reactions, NAD must be permanently resynthesized. Nicotinamide and nicotinic acid as well as nicotinamide riboside (NR) and nicotinic acid riboside (NAR) are the major precursors for NAD biosynthesis in humans. In this study, we explored whether the ribosides NR and NAR can be generated in human cells. We demonstrate that purified, recombinant human cytosolic 5'-nucleotidases (5'-NTs) CN-II and CN-III, but not CN-IA, can dephosphorylate the mononucleotides nicotinamide mononucleotide and nicotinic acid mononucleotide (NAMN) and thus catalyze NR and NAR formation in vitro...
November 6, 2015: Journal of Biological Chemistry
B Vitali, F Cruciani, G Picone, C Parolin, G Donders, L Laghi
In this study, we sought to find novel bacterial and metabolic hallmarks for bacterial vaginosis (BV). We studied the vaginal microbiome and metabolome of vaginal fluids from BV-affected patients (n = 43) and healthy controls (n = 37) by means of an integrated approach based on quantitative polymerase chain reaction (qPCR) and proton nuclear magnetic resonance ((1)H-NMR). The correlations between the clinical condition and vaginal bacterial communities were investigated by principal component analysis (PCA)...
December 2015: European Journal of Clinical Microbiology & Infectious Diseases
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