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NAD+ AND nicotinic acid

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https://www.readbyqxmd.com/read/28388636/characterization-and-mutational-analysis-of-a-nicotinamide-mononucleotide-deamidase-from-agrobacterium-tumefaciens-showing-high-thermal-stability-and-catalytic-efficiency
#1
Ana Belén Martínez-Moñino, Rubén Zapata-Pérez, Antonio Ginés García-Saura, Fernando Gil-Ortiz, Manuela Pérez-Gilabert, Álvaro Sánchez-Ferrer
NAD+ has emerged as a crucial element in both bioenergetic and signaling pathways since it acts as a key regulator of cellular and organismal homeostasis. Among the enzymes involved in its recycling, nicotinamide mononucleotide (NMN) deamidase is one of the key players in the bacterial pyridine nucleotide cycle, where it catalyzes the conversion of NMN into nicotinic acid mononucleotide (NaMN), which is later converted to NAD+ in the Preiss-Handler pathway. The biochemical characteristics of bacterial NMN deamidases have been poorly studied, although they have been investigated in some firmicutes, gamma-proteobacteria and actinobacteria...
2017: PloS One
https://www.readbyqxmd.com/read/28374531/from-nad-to-ni-pincer-complex-a-significant-cofactor-evolution-presented-by-lactate-racemase
#2
Ming-Jia Yu, Shi-Lu Chen
Lactate racemase (LarA), a new Ni enzyme discovered recently, catalyzes the racemization between D- and L-lactates via a novel Ni pincer cofactor (Ni-PTTMN) derived from nicotinic acid. Here, using DFT and a 200-atom active-site model, LarA is revealed to employ a modified proton-coupled hydride transfer mechanism where a hydride is transferred to a cofactor pyridine carbon from the substrate α-carbon along with a proton transfer from the substrate hydroxyl to a histidine, and then moved back from the opposite side...
April 4, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28337428/niacin-mediated-gene-expression-and-role-of-niar-as-a-transcriptional-repressor-of-niax-nadc-and-pnuc-in-streptococcus-pneumoniae
#3
Muhammad Afzal, Oscar P Kuipers, Sulman Shafeeq
NAD (Nicotinamide Adenine Dinucleotide) biosynthesis is vital for bacterial physiology and plays an important role in cellular metabolism. A naturally occurring vitamin B complex, niacin (nicotinic acid), is a precursor of coenzymes NAD and NADP. Here, we study the impact of niacin on global gene expression of Streptococcus pneumoniae D39 and elucidate the role of NiaR as a transcriptional regulator of niaX, nadC, and pnuC. Transcriptome comparison of the D39 wild-type grown in chemically defined medium (CDM) with 0 to 10 mM niacin revealed elevated expression of various genes, including niaX, nadC, pnuC, fba, rex, gapN, pncB, gap, adhE, and adhB2 that are putatively involved in the transport and utilization of niacin...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28216063/the-nad-precursor-nicotinic-acid-improves-genomic-integrity-in-human-peripheral-blood-mononuclear-cells-after-x-irradiation
#4
Kathrin Weidele, Sascha Beneke, Alexander Bürkle
NAD(+) is an essential cofactor for enzymes catalyzing redox-reactions as well as an electron carrier in energy metabolism. Aside from this, NAD(+) consuming enzymes like poly(ADP-ribose) polymerases and sirtuins are important regulators involved in chromatin-restructuring processes during repair and epigenetics/transcriptional adaption. In order to replenish cellular NAD(+) levels after cleavage, synthesis starts from precursors such as nicotinamide, nicotinamide riboside or nicotinic acid to match the need for this essential molecule...
February 13, 2017: DNA Repair
https://www.readbyqxmd.com/read/28018295/combined-whole-cell-high-throughput-functional-screening-for-identification-of-new-nicotinamidases-pyrazinamidases-in-metagenomic-polygenomic-libraries
#5
Rubén Zapata-Pérez, Antonio G García-Saura, Mohamed Jebbar, Peter N Golyshin, Álvaro Sánchez-Ferrer
Nicotinamidases catalyze the hydrolysis of the amide bond in nicotinamide (NAM) to produce ammonia and nicotinic acid (NA). These enzymes are an essential component of the NAD(+) salvage pathway and are implicated in the viability of several pathogenic organisms. Its absence in humans makes them a promising drug target. In addition, although they are key analytical biocatalysts for screening modulators in relevant biomedical enzymes, such as sirtuins and poly-ADP-ribosyltransferases, no commercial sources are available...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/27984041/structural-and-functional-characterization-of-plasmodium-falciparum-nicotinic-acid-mononucleotide-adenylyltransferase
#6
Jochen Bathke, Karin Fritz-Wolf, Christina Brandstädter, Anja Burkhardt, Esther Jortzik, Stefan Rahlfs, Katja Becker
Nicotinic acid mononucleotide adenylyltransferase (NaMNAT) is an indispensable enzyme for the synthesis of NAD and NADP. It catalyzes the adenylylation of nicotinic acid mononucleotide (NaMN) to yield nicotinic acid adenine dinucleotide (NaAD). Since NAD(H) and NADP(H) are essentially involved in metabolic and redox regulatory reactions, NaMNAT is an attractive drug target in the fight against bacterial and parasitic infections. Notably, NaMNAT of the malaria parasite Plasmodium falciparum possesses only 20% sequence identity with the homologous human enzyme...
October 27, 2016: Journal of Molecular Biology
https://www.readbyqxmd.com/read/27939939/cd38-in-the-pathogenesis-of-allergic-airway-disease-potential-therapeutic-targets
#7
REVIEW
Deepak A Deshpande, Alonso G P Guedes, Frances E Lund, Subbaya Subramanian, Timothy F Walseth, Mathur S Kannan
CD38 is an ectoenzyme that catalyzes the conversion of β-nicotinamide adenine dinucleotide (β-NAD) to cyclic adenosine diphosphoribose (cADPR) and adenosine diphosphoribose (ADPR) and NADP to nicotinic acid adenine dinucleotide phosphate (NAADP) and adenosine diphosphoribose-2'-phosphate (ADPR-P). The metabolites of NAD and NADP have roles in calcium signaling in different cell types including airway smooth muscle (ASM) cells. In ASM cells, inflammatory cytokines augment CD38 expression and to a greater magnitude in cells from asthmatics, indicating a greater capacity for the generation of cADPR and ADPR in ASM from asthmatics...
April 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27783449/essential-role-of-bordetella-nadc-in-a-quinolinate-salvage-pathway-for-nad-biosynthesis
#8
Timothy J Brickman, Ryan J Suhadolc, Pamela J McKelvey, Sandra K Armstrong
Nicotinamide adenine dinucleotide (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
https://www.readbyqxmd.com/read/27783203/cardiotoxicity-associated-with-nicotinamide-phosphoribosyltransferase-inhibitors-in-rodents-and-in-rat-and-human-derived-cells-lines
#9
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
https://www.readbyqxmd.com/read/27725675/nrk1-controls-nicotinamide-mononucleotide-and-nicotinamide-riboside-metabolism-in-mammalian-cells
#10
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
https://www.readbyqxmd.com/read/27721479/nicotinamide-riboside-is-uniquely-and-orally-bioavailable-in-mice-and-humans
#11
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
https://www.readbyqxmd.com/read/27621317/3-nadp-and-3-naadp-two-metabolites-formed-by-the-bacterial-type-iii-effector-avrrxo1
#12
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
https://www.readbyqxmd.com/read/27616477/naxe-mutations-disrupt-the-cellular-nad-p-hx-repair-system-and-cause-a-lethal-neurometabolic-disorder-of-early-childhood
#13
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
https://www.readbyqxmd.com/read/27451449/the-riemerella-anatipestifer-as87_01735-gene-encodes-nicotinamidase-pnca-an-important-virulence-factor
#14
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
https://www.readbyqxmd.com/read/27448710/the-expression-of-cg9940-affects-the-adaptation-of-cardiac-function-mobility-and-lifespan-to-exercise-in-aging-drosophila
#15
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
https://www.readbyqxmd.com/read/27374990/nad-metabolism-bioenergetics-signaling-and-manipulation-for-therapy
#16
REVIEW
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
https://www.readbyqxmd.com/read/27218267/structural-and-biochemical-characterization-of-6-hydroxynicotinic-acid-3-monooxygenase-a-novel-decarboxylative-hydroxylase-involved-in-aerobic-nicotinate-degradation
#17
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
https://www.readbyqxmd.com/read/27052539/nicotinamide-riboside-is-a-major-nad-precursor-vitamin-in-cow-milk
#18
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
https://www.readbyqxmd.com/read/27048556/nicotinic-acid-supplementation-in-diet-favored-intramuscular-fat-deposition-and-lipid-metabolism-in-finishing-steers
#19
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
https://www.readbyqxmd.com/read/26805589/structural-insights-into-the-quaternary-catalytic-mechanism-of-hexameric-human-quinolinate-phosphoribosyltransferase-a-key-enzyme-in-de-novo-nad-biosynthesis
#20
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...
January 25, 2016: Scientific Reports
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