2.0 2012-05-31 13:47:00 -0600 2015-06-03 15:53:49 -0600 ECMDB01179 M2MDB000286 Nicotinic acid adenine dinucleotide Nicotinic acid adenine dinucleotide phosphate, (NAADP), is a Ca2+-mobilizing second messenger synthesized in response to extracellular stimuli. NAADP binds to and opens Ca2+ channels on intracellular organelles, thereby increasing the intracellular Ca2+ concentration which, in turn, modulates a variety of cellular processes. Structurally, it is a dinucleotide that only differs from the house-keeping enzyme cofactor, NADP by a hydroxyl group (replacing the nicotinamide amino group) and yet this minor modification converts it into the most potent Ca2+-mobilizing second messenger yet described. Deamido-NAD Deamido-NAD+ Deamido-NAD⁺ Deamidonicotinamide adenine dinucleoetide Deamino-nad+ NAAD NaADN NAADP Nicotinate adenine dinucleotide Nicotinate adenine dinucleotide phosphate Nicotinic acid adenine dinucleotide Nicotinic acid adenine dinucleotide phosphate Nicotinic acid adenine dinucleotide phosphoric acid C21H27N6O15P2 665.4178 665.100962248 1-[(2R,3R,4S,5R)-5-[({[({[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy}(hydroxy)phosphoryl)oxy](hydroxy)phosphoryl}oxy)methyl]-3,4-dihydroxyoxolan-2-yl]-3-carboxy-1lambda5-pyridin-1-ylium 1-[(2R,3R,4S,5R)-5-{[({[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy(hydroxy)phosphoryl}oxy(hydroxy)phosphoryl)oxy]methyl}-3,4-dihydroxyoxolan-2-yl]-3-carboxy-1lambda5-pyridin-1-ylium 6450-77-7 NC1=C2N=CN([C@@H]3O[C@H](COP(O)(=O)OP(O)(=O)OC[C@H]4O[C@H]([C@H](O)[C@@H]4O)[N+]4=CC=CC(=C4)C(O)=O)[C@@H](O)[C@H]3O)C2=NC=N1 InChI=1S/C21H26N6O15P2/c22-17-12-18(24-7-23-17)27(8-25-12)20-16(31)14(29)11(41-20)6-39-44(36,37)42-43(34,35)38-5-10-13(28)15(30)19(40-10)26-3-1-2-9(4-26)21(32)33/h1-4,7-8,10-11,13-16,19-20,28-31H,5-6H2,(H4-,22,23,24,32,33,34,35,36,37)/p+1/t10-,11-,13-,14-,15-,16-,19-,20-/m1/s1 SENPVEZBRZQVST-HISDBWNOSA-O Solid Cytosol logp -0.89 ALOGPS logs -2.57 ALOGPS solubility 1.88e+00 g/l ALOGPS logp -9.1 ChemAxon pka_strongest_acidic 1.8 ChemAxon pka_strongest_basic 4.03 ChemAxon iupac 1-[(2R,3R,4S,5R)-5-[({[({[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy}(hydroxy)phosphoryl)oxy](hydroxy)phosphoryl}oxy)methyl]-3,4-dihydroxyoxolan-2-yl]-3-carboxy-1lambda5-pyridin-1-ylium ChemAxon average_mass 665.4178 ChemAxon mono_mass 665.100962248 ChemAxon smiles NC1=C2N=CN([C@@H]3O[C@H](COP(O)(=O)OP(O)(=O)OC[C@H]4O[C@H]([C@H](O)[C@@H]4O)[N+]4=CC=CC(=C4)C(O)=O)[C@@H](O)[C@H]3O)C2=NC=N1 ChemAxon formula C21H27N6O15P2 ChemAxon inchi InChI=1S/C21H26N6O15P2/c22-17-12-18(24-7-23-17)27(8-25-12)20-16(31)14(29)11(41-20)6-39-44(36,37)42-43(34,35)38-5-10-13(28)15(30)19(40-10)26-3-1-2-9(4-26)21(32)33/h1-4,7-8,10-11,13-16,19-20,28-31H,5-6H2,(H4-,22,23,24,32,33,34,35,36,37)/p+1/t10-,11-,13-,14-,15-,16-,19-,20-/m1/s1 ChemAxon inchikey SENPVEZBRZQVST-HISDBWNOSA-O ChemAxon polar_surface_area 312.47 ChemAxon refractivity 140.17 ChemAxon polarizability 58.09 ChemAxon rotatable_bond_count 11 ChemAxon acceptor_count 16 ChemAxon donor_count 8 ChemAxon physiological_charge -2 ChemAxon formal_charge 1 ChemAxon Nitrogen metabolism The biological process of the nitrogen cycle is a complex interplay among many microorganisms catalyzing different reactions, where nitrogen is found in various oxidation states ranging from +5 in nitrate to -3 in ammonia. The ability of fixing atmospheric nitrogen by the nitrogenase enzyme complex is present in restricted prokaryotes (diazotrophs). The other reduction pathways are assimilatory nitrate reduction and dissimilatory nitrate reduction both for conversion to ammonia, and denitrification. Denitrification is a respiration in which nitrate or nitrite is reduced as a terminal electron acceptor under low oxygen or anoxic conditions, producing gaseous nitrogen compounds (N2, NO and N2O) to the atmosphere. Nitrate can be introduced into the cytoplasm through a nitrate:nitrite antiporter NarK or a nitrate / nitrite transporter NarU. Nitrate is then reduced by a Nitrate Reductase resulting in the release of water, an acceptor and a Nitrite. Nitrite can also be introduced into the cytoplasm through a nitrate:nitrite antiporter NarK Nitrite can be reduced a NADPH dependent nitrite reductase resulting in water and NAD and Ammonia. Nitrite can interact with hydrogen ion, ferrocytochrome c through a cytochrome c-552 ferricytochrome resulting in the release of ferricytochrome c, water and ammonia Another process by which ammonia is produced is by a reversible reaction of hydroxylamine with a reduced acceptor through a hydroxylamine reductase resulting in an acceptor, water and ammonia. Water and carbon dioxide react through a carbonate dehydratase resulting in carbamic acid. This compound reacts spontaneously with hydrogen ion resulting in the release of carbon dioxide and ammonia. Carbon dioxide can interact with water through a carbonic anhydrase resulting in hydrogen carbonate. This compound interacts with cyanate and hydrogen ion through a cyanate hydratase resulting in a carbamic acid. Ammonia can be metabolized by reacting with L-glutamine and ATP driven glutamine synthetase resulting in ADP, phosphate and L-glutamine. The latter compound reacts with oxoglutaric acid and hydrogen ion through a NADPH dependent glutamate synthase resulting in the release of NADP and L-glutamic acid. L-glutamic acid reacts with water through a NADP-specific glutamate dehydrogenase resulting in the release of oxoglutaric acid, NADPH, hydrogen ion and ammonia. PW000755 ec00910 Metabolic Nicotinate and nicotinamide metabolism ec00760 Metabolic pathways eco01100 NAD biosynthesis Nicotinamide adenine dinucleotide (NAD) can be biosynthesized from L-aspartic acid.This amino acid reacts with oxygen through an L-aspartate oxidase resulting in a hydrogen ion, hydrogen peroxide and an iminoaspartic acid. The latter compound interacts with dihydroxyacetone phosphate through a quinolinate synthase A, resulting in a phosphate, water, and a quinolic acid. Quinolic acid interacts with phosphoribosyl pyrophosphate and hydrogen ion through a quinolinate phosphoribosyltransferase resulting in pyrophosphate, carbon dioxide and nicotinate beta-D-ribonucleotide. This last compound is adenylated through an ATP driven nicotinate-mononucleotide adenylyltransferase releasing a pyrophosphate and resulting in a nicotinic acid adenine dinucleotide. Nicotinic acid adenine dinucleotide is processed through an NAD synthetase, NH3-dependent in two different manners. In the first case, Nicotinic acid adenine dinucleotide interacts with ATP, L-glutamine and water through the enzyme and results in hydrogen ion, AMP, pyrophosphate, L-glutamic acid and NAD. In the second case, Nicotinic acid adenine dinucleotide interacts with ATP and ammonium through the enzyme resulting in a pyrophosphate, AMP, hydrogen ion and NAD. NAD then proceeds to regulate its own pathway by repressing L-aspartate oxidase. As a general rule, most prokaryotes utilize the aspartate de novo pathway, in which the nicotinate moiety of NAD is synthesized from aspartate , while in eukaryotes, the de novo pathway starts with tryptophan. PW000829 Metabolic NAD salvage Even though NAD molecules are not consumed during oxidation reactions, they have a relatively short half-life. For example, in E. coli the NAD+ half-life is 90 minutes. Once enzymatically degraded, the pyrimidine moiety of the molecule can be recouped via the NAD salvage cycles. This pathway is used for two purposes: it recycles the internally degraded NAD products nicotinamide D-ribonucleotide (also known as nicotinamide mononucleotide, or NMN) and nicotinamide, and it is used for the assimilation of exogenous NAD+. NAD reacts spontaneously with water resulting in the release of hydrogen ion, AMP and beta-nicotinamide D-ribonucleotide. This enzyme can either interact spontaneously with water resulting in the release of D-ribofuranose 5-phosphate, hydrogen ion and Nacinamide. On the other hand beta-nicotinamide D-ribonucleotide can also react with water through NMN amidohydrolase resulting in ammonium, and Nicotinate beta-D-ribonucleotide. Also it can interact with water spontaneously resulting in the release of phosphate resulting in a Nicotinamide riboside. Niacinamide interacts with water through a nicotinamidase resulting in a release of ammonium and nicotinic acid. This compound interacts with water and phosphoribosyl pyrophosphate through an ATP driven nicotinate phosphoribosyltransferase resulting in the release of ADP, pyrophosphate and phosphate and nicotinate beta-D-ribonucleotide. Nicotinamide riboside interacts with an ATP driven NadR DNA-binding transcriptional repressor and NMN adenylyltransferase (Escherichia coli) resulting in a ADP, hydrogen ion and beta-nicotinamide D-ribonucleotide. This compound interacts with ATP and hydrogen ion through NadR DNA-binding transcriptional repressor and NMN adenylyltransferase resulting in pyrophosphate and NAD. Nicotinate beta-D-ribonucleotide is adenylated through the interaction with ATP and a hydrogen ion through a nicotinate-mononucleotide adenylyltransferase resulting in pyrophosphate and Nicotinic acid adenine dinucleotide. Nicotinic acid adenine dinucleotide interacts with L-glutamine and water through an ATP driven NAD synthetase, NH3-dependent resulting in AMP, pyrophosphate, hydrogen ion, L-glutamic acid and NAD. PW000830 Metabolic NAD salvage pathway I PYRIDNUCSAL-PWY NAD biosynthesis I (from aspartate) PYRIDNUCSYN-PWY Specdb::CMs 22009 Specdb::CMs 676483 Specdb::CMs 676484 Specdb::CMs 676485 Specdb::CMs 676486 Specdb::CMs 676487 Specdb::CMs 676488 Specdb::CMs 676489 Specdb::CMs 676490 Specdb::CMs 676491 Specdb::CMs 676492 Specdb::CMs 676493 Specdb::CMs 676494 Specdb::CMs 676495 Specdb::CMs 676496 Specdb::CMs 676497 Specdb::CMs 676498 Specdb::CMs 676499 Specdb::CMs 676500 Specdb::CMs 676501 Specdb::CMs 676502 Specdb::CMs 676503 Specdb::CMs 676504 Specdb::CMs 676505 Specdb::CMs 676506 Specdb::NmrOneD 8822 Specdb::NmrOneD 8823 Specdb::NmrOneD 8824 Specdb::NmrOneD 8825 Specdb::NmrOneD 8826 Specdb::NmrOneD 8827 Specdb::NmrOneD 8828 Specdb::NmrOneD 8829 Specdb::NmrOneD 8830 Specdb::NmrOneD 8831 Specdb::NmrOneD 8832 Specdb::NmrOneD 8833 Specdb::NmrOneD 8834 Specdb::NmrOneD 8835 Specdb::NmrOneD 8836 Specdb::NmrOneD 8837 Specdb::NmrOneD 8838 Specdb::NmrOneD 8839 Specdb::NmrOneD 8840 Specdb::NmrOneD 8841 Specdb::MsMs 26984 Specdb::MsMs 26985 Specdb::MsMs 26986 Specdb::MsMs 33542 Specdb::MsMs 33543 Specdb::MsMs 33544 Specdb::MsMs 2309433 Specdb::MsMs 2309434 Specdb::MsMs 2309435 HMDB01179 165490 145043 C00857 DEAMIDO-NAD NXX NAADP Keseler, I. M., Collado-Vides, J., Santos-Zavaleta, A., Peralta-Gil, M., Gama-Castro, S., Muniz-Rascado, L., Bonavides-Martinez, C., Paley, S., Krummenacker, M., Altman, T., Kaipa, P., Spaulding, A., Pacheco, J., Latendresse, M., Fulcher, C., Sarker, M., Shearer, A. G., Mackie, A., Paulsen, I., Gunsalus, R. P., Karp, P. D. (2011). "EcoCyc: a comprehensive database of Escherichia coli biology." Nucleic Acids Res 39:D583-D590. 21097882 Kanehisa, M., Goto, S., Sato, Y., Furumichi, M., Tanabe, M. (2012). "KEGG for integration and interpretation of large-scale molecular data sets." Nucleic Acids Res 40:D109-D114. 22080510 van der Werf, M. J., Overkamp, K. M., Muilwijk, B., Coulier, L., Hankemeier, T. (2007). "Microbial metabolomics: toward a platform with full metabolome coverage." Anal Biochem 370:17-25. 17765195 Winder, C. L., Dunn, W. B., Schuler, S., Broadhurst, D., Jarvis, R., Stephens, G. M., Goodacre, R. (2008). "Global metabolic profiling of Escherichia coli cultures: an evaluation of methods for quenching and extraction of intracellular metabolites." Anal Chem 80:2939-2948. 18331064 Nicotinate-nucleotide adenylyltransferase P0A752 NADD_ECOLI nadD http://ecmdb.ca/proteins/P0A752.xml NH(3)-dependent NAD(+) synthetase P18843 NADE_ECOLI nadE http://ecmdb.ca/proteins/P18843.xml Transcriptional regulator nadR P27278 NADR_ECOLI nadR http://ecmdb.ca/proteins/P27278.xml NADH pyrophosphatase P32664 NUDC_ECOLI nudC http://ecmdb.ca/proteins/P32664.xml Adenosine triphosphate + Hydrogen ion + Nicotinamide ribotide <> Nicotinic acid adenine dinucleotide + Pyrophosphate R03005 NICONUCADENYLYLTRAN-RXN Adenosine triphosphate + Nicotinic acid adenine dinucleotide + Ammonium > Adenosine monophosphate + Hydrogen ion + NAD + Pyrophosphate Adenosine triphosphate + Nicotinic acid adenine dinucleotide + Ammonia <> Adenosine monophosphate + Pyrophosphate + NAD R00189 NAD-SYNTH-NH3-RXN Nicotinic acid adenine dinucleotide + Water <> Adenosine monophosphate + Nicotinamide ribotide R03004 Adenosine triphosphate + Nicotinamide ribotide <> Pyrophosphate + Nicotinic acid adenine dinucleotide R03005 Adenosine triphosphate + Nicotinic acid adenine dinucleotide + L-Glutamine + Water > Hydrogen ion + Adenosine monophosphate + Pyrophosphate + NAD + L-Glutamate NAD-SYNTH-GLN-RXN Adenosine triphosphate + Nicotinic acid adenine dinucleotide + Ammonia > Adenosine monophosphate + Pyrophosphate + NAD NAD-SYNTH-NH3-RXN Hydrogen ion + Adenosine triphosphate + Nicotinamide ribotide > Pyrophosphate + Nicotinic acid adenine dinucleotide NICONUCADENYLYLTRAN-RXN Adenosine triphosphate + Nicotinamide ribotide > Pyrophosphate + Nicotinic acid adenine dinucleotide nicotinate beta-D-ribonucleotide + Adenosine triphosphate + Hydrogen ion + Nicotinamide ribotide > Pyrophosphate + Nicotinic acid adenine dinucleotide PW_R003010 Nicotinic acid adenine dinucleotide + Water + L-Glutamine + Adenosine triphosphate > Hydrogen ion + Adenosine monophosphate + Pyrophosphate + L-Glutamic acid + NAD + L-Glutamate PW_R003011 Nicotinic acid adenine dinucleotide + Adenosine triphosphate + Ammonium > Hydrogen ion + Adenosine monophosphate + Pyrophosphate + NAD PW_R003012 Adenosine triphosphate + Nicotinic acid adenine dinucleotide + Ammonia <> Adenosine monophosphate + Pyrophosphate + NAD