2.02012-05-31 13:53:23 -06002015-09-13 12:56:11 -0600ECMDB01488M2MDB000399Nicotinic acidNicotinic acid, also known as niacin or vitamin B3, is a derivative of pyridine, with a carboxyl group (COOH) at the 3-position. Other forms of vitamin B3 include the corresponding amide, nicotinamide ("niacinamide"), where the carboxyl group has been replaced by a carboxamide group (CONH2), as well as more complex amides and a variety of esters. The uptake of nicotinic acid by Escherichia coli is dependent on the presence of the enzyme nicotinic acid phosphoribosyl transferase and a source of energy.3-Carboxylpyridine3-Carboxypyridine3-Pyridinecarboxylate3-Pyridinecarboxylic acid3-Pyridylcarboxylate3-Pyridylcarboxylic acidAkotinApelagrinDaskilEfacinEnduracinLinicNiacNiacinNiacineNiacorNicacidNicaminNicanginNico-400-Nico-SpanNicobidNicocapNicodelmineNicolarNiconacidNicosan 3NicotinateNicotinic acidNicotinipcaNicylNyclinPellagrinPeloninSlo-niacinVitamin B3Vitamin B<sub>3</sub>WampocapC6H5NO2123.1094123.032028409pyridine-3-carboxylic acidniacin59-67-6OC(=O)C1=CN=CC=C1InChI=1S/C6H5NO2/c8-6(9)5-2-1-3-7-4-5/h1-4H,(H,8,9)PVNIIMVLHYAWGP-UHFFFAOYSA-NSolidCytosolExtra-organismPeriplasmlogp0.29logs-0.17solubility8.31e+01 g/lmelting_point236.6 oClogp-0.17pka_strongest_acidic2.79pka_strongest_basic4.19iupacpyridine-3-carboxylic acidaverage_mass123.1094mono_mass123.032028409smilesOC(=O)C1=CN=CC=C1formulaC6H5NO2inchiInChI=1S/C6H5NO2/c8-6(9)5-2-1-3-7-4-5/h1-4H,(H,8,9)inchikeyPVNIIMVLHYAWGP-UHFFFAOYSA-Npolar_surface_area50.19refractivity31.16polarizability11.3rotatable_bond_count1acceptor_count3donor_count1physiological_charge-1formal_charge0Porphyrin and chlorophyll metabolismec00860Nicotinate and nicotinamide metabolismec00760Riboflavin metabolismec00740Metabolic pathwayseco01100NAD salvageEven 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.
PW000830Metabolicadenosylcobalamin salvage from cobinamideCobinamide is incorporated from the extracellular space through a transport system into the cytosol. Once inside the cytosol, cobinamide interacts with ATP through a cobinamide adenosyl transferase resulting in the release of a triphosphate and an adenosylcobinamide. The latter compound is then phosphorylated through an ATP-dependent cobinamide kinase resulting in the release of ADP, a hydrogen ion and adenosyl-cobinamide phosphate. This last compound then interacts with GTP and a hydrogen ion through a cobinamide-P guanylyltransferase resulting in the release of a pyrophosphate and an adenosylcobinamide-GDP.
A dimethylbenzimidazole interacts with a nicotinate D-ribonucleotide through a nicotinate-nucleotide dimethylbenzumidazole phosphoribosyltransferase resulting in the release of a nicotinate, a hydrogen ion and an alpha-ribazole 5' phosphate.
The adenosylcobinamide-GDP and the alpha-ribazole 5' phosphate interact together through a cobalamin 5' phosphate synthase resulting in the release of a hydrogen ion, a GMP and Adenosylcobalamin 5'-phosphate. The latter compound then interacts with a water molecule through an adenosylcbalamin 5' phosphate phosphatase resulting in the release of a phosphate and a coenzyme B12.
Likewise a cobalamin molecule can interact with ATP through a cobalamin adenosyltransferase resulting in the release of a triphosphate and a coenzyme B12PW001884MetabolicNAD salvage pathway IPYRIDNUCSAL-PWYadenosylcobalamin salvage from cobinamide ICOBALSYN-PWY-1Specdb::CMs754Specdb::CMs755Specdb::CMs756Specdb::CMs757Specdb::CMs1037Specdb::CMs2756Specdb::CMs27987Specdb::CMs30223Specdb::CMs30321Specdb::CMs30648Specdb::CMs30893Specdb::CMs31339Specdb::CMs32373Specdb::CMs38091Specdb::CMs132627Specdb::CMs140361Specdb::EiMs446Specdb::NmrOneD1716Specdb::NmrOneD2514Specdb::NmrOneD3213Specdb::NmrOneD4801Specdb::NmrOneD4802Specdb::NmrOneD147860Specdb::NmrOneD147861Specdb::NmrOneD147862Specdb::NmrOneD147863Specdb::NmrOneD147864Specdb::NmrOneD147865Specdb::NmrOneD147866Specdb::NmrOneD147867Specdb::NmrOneD147868Specdb::NmrOneD147869Specdb::NmrOneD147870Specdb::NmrOneD147871Specdb::NmrOneD147872Specdb::NmrOneD147873Specdb::NmrOneD147874Specdb::NmrOneD147875Specdb::NmrOneD147876Specdb::NmrOneD147877Specdb::NmrOneD147878Specdb::NmrOneD147879Specdb::MsMs1604Specdb::MsMs1605Specdb::MsMs1606Specdb::MsMs5336Specdb::MsMs5337Specdb::MsMs5338Specdb::MsMs5339Specdb::MsMs5340Specdb::MsMs5341Specdb::MsMs5342Specdb::MsMs5343Specdb::MsMs5344Specdb::MsMs5345Specdb::MsMs5346Specdb::MsMs5351Specdb::MsMs5352Specdb::MsMs5353Specdb::MsMs178800Specdb::MsMs178801Specdb::MsMs178802Specdb::MsMs181119Specdb::MsMs181120Specdb::MsMs181121Specdb::MsMs438191Specdb::MsMs438192Specdb::NmrTwoD1075Specdb::NmrTwoD1656HMDB01488938913C0025315940NIACINENIONicotinic acidKeseler, 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-D590.21097882Kanehisa, 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-D114.22080510van 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 370:17-25.17765195Winder, 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 80:2939-2948.18331064Dastur DK, Santhadevi N, Quadros EV, Avari FC, Wadia NH, Desai MN, Bharucha EP: The B-vitamins in malnutrition with alcoholism. A model of intervitamin relationships. Br J Nutr. 1976 Sep;36(2):143-59.182198Tunaru S, Kero J, Schaub A, Wufka C, Blaukat A, Pfeffer K, Offermanns S: PUMA-G and HM74 are receptors for nicotinic acid and mediate its anti-lipolytic effect. Nat Med. 2003 Mar;9(3):352-5. Epub 2003 Feb 3.12563315Salvi A, Carrupt PA, Mayer JM, Testa B: Esterase-like activity of human serum albumin toward prodrug esters of nicotinic acid. Drug Metab Dispos. 1997 Apr;25(4):395-8.9107536Hertle H, Kiese M, Renner G: Absorption in rats, dogs, pigs, and humans of nicotinic acid after oral administration of phosphatidyl inositol pentanicotinate hydrochloride (PIN). Arzneimittelforschung. 1979;29(1):114-6.582105Zarzycki PK, Kowalski P, Nowakowska J, Lamparczyk H: High-performance liquid chromatographic and capillary electrophoretic determination of free nicotinic acid in human plasma and separation of its metabolites by capillary electrophoresis. J Chromatogr A. 1995 Aug 11;709(1):203-8.7581845Hengen N, Seiberth V, Hengen M: High-performance liquid-chromatographic determination of free nicotinic acid and its metabolite, nicotinuric acid, in plasma and urine. Clin Chem. 1978 Oct;24(10):1740-3.699281Santos RD: [Pharmacology of niacin or nicotinic acid] Arq Bras Cardiol. 2005 Oct;85 Suppl 5:17-9. Epub 2006 Jan 2.16400392Mrochek JE, Jolley RL, Young DS, Turner WJ: Metabolic response of humans to ingestion of nicotinic acid and nicotinamide. Clin Chem. 1976 Nov;22(11):1821-7.135660Pike NB: Flushing out the role of GPR109A (HM74A) in the clinical efficacy of nicotinic acid. J Clin Invest. 2005 Dec;115(12):3400-3.16322787Kobayashi M, Shimizu S: [Nicotinic acid and nicotinamide] Nippon Rinsho. 1999 Oct;57(10):2211-7.10540864Sutherland WH, Larking PW, Nye ER: Modification of nicotinic acid and prostaglandin E1 antilipolytic action in vitro. Atherosclerosis. 1976 Oct;25(1):45-53.186078Stratford MR, Dennis MF, Hoskin P, Phillips H, Hodgkiss RJ, Rojas A: Nicotinamide pharmacokinetics in humans: effect of gastric acid inhibition, comparison of rectal vs oral administration and the use of saliva for drug monitoring. Br J Cancer. 1996 Jul;74(1):16-21.8679452Angelin B, Einarsson K, Leijd B: Biliary lipid composition during treatment with different hypolipidaemic drugs. Eur J Clin Invest. 1979 Jun;9(3):185-90.113218Patterson MC, Di Bisceglie AM, Higgins JJ, Abel RB, Schiffmann R, Parker CC, Argoff CE, Grewal RP, Yu K, Pentchev PG, et al.: The effect of cholesterol-lowering agents on hepatic and plasma cholesterol in Niemann-Pick disease type C. Neurology. 1993 Jan;43(1):61-4.8423912Muller B, Kasper M, Surber C, Imanidis G: Permeation, metabolism and site of action concentration of nicotinic acid derivatives in human skin. Correlation with topical pharmacological effect. Eur J Pharm Sci. 2003 Oct;20(2):181-95.14550884Chekalina SI, Guseva LI, Bardyechev MS: [Use of nicotinic acid and midocalm for correcting blood coagulation in patients with radiation edema of the extremities] Med Radiol (Mosk). 1985 Aug;30(8):28-30.4033386Gopal E, Fei YJ, Miyauchi S, Zhuang L, Prasad PD, Ganapathy V: Sodium-coupled and electrogenic transport of B-complex vitamin nicotinic acid by slc5a8, a member of the Na/glucose co-transporter gene family. Biochem J. 2005 May 15;388(Pt 1):309-16.15651982McElvain, S. M.; Goese, M. A. Preparation of nicotinic acid from pyridine. Journal of the American Chemical Society (1941), 63 2283-4.http://hmdb.ca/system/metabolites/msds/000/001/350/original/HMDB01488.pdf?1358461732Purine nucleoside phosphorylase deoD-typeP0ABP8DEOD_ECOLIdeoDhttp://ecmdb.ca/proteins/P0ABP8.xmlNicotinate phosphoribosyltransferaseP18133PNCB_ECOLIpncBhttp://ecmdb.ca/proteins/P18133.xmlPyrazinamidase/nicotinamidaseP21369PNCA_ECOLIpncAhttp://ecmdb.ca/proteins/P21369.xmlNicotinate-nucleotide--dimethylbenzimidazole phosphoribosyltransferaseP36562COBT_ECOLIcobThttp://ecmdb.ca/proteins/P36562.xmlOuter membrane protein NP77747OMPN_ECOLIompNhttp://ecmdb.ca/proteins/P77747.xmlOuter membrane pore protein EP02932PHOE_ECOLIphoEhttp://ecmdb.ca/proteins/P02932.xmlOuter membrane protein FP02931OMPF_ECOLIompFhttp://ecmdb.ca/proteins/P02931.xmlOuter membrane protein CP06996OMPC_ECOLIompChttp://ecmdb.ca/proteins/P06996.xmlAdenosine triphosphate + Water + Nicotinic acid + Phosphoribosyl pyrophosphate > ADP + Nicotinamide ribotide + Phosphate + PyrophosphateWater + Niacinamide > Nicotinic acid + AmmoniumDimethylbenzimidazole + Nicotinamide ribotide <> N1-(5-Phospho-a-D-ribosyl)-5,6-dimethylbenzimidazole + Hydrogen ion + Nicotinic acidR04148DMBPPRIBOSYLTRANS-RXNNiacinamide + Water <> Nicotinic acid + AmmoniaR01268Nicotinamide ribotide + Pyrophosphate + Adenosine triphosphate + Water <> Nicotinic acid + Phosphoribosyl pyrophosphate + ADP + PhosphateR01724Nicotinate D-ribonucleoside + Phosphate <> Nicotinic acid + alpha-D-Ribose 1-phosphate + Hydrogen ionR02295Nicotinamide ribotide + Dimethylbenzimidazole > Hydrogen ion + Nicotinic acid + N1-(5-Phospho-a-D-ribosyl)-5,6-dimethylbenzimidazoleDMBPPRIBOSYLTRANS-RXNNiacinamide + Water > Hydrogen ion + Nicotinic acid + AmmoniaR01268NICOTINAMID-RXNNicotinamide ribotide + Pyrophosphate < Hydrogen ion + Nicotinic acid + Phosphoribosyl pyrophosphateR01724NICOTINATEPRIBOSYLTRANS-RXNNicotinamide ribotide + Dimethylbenzimidazole > Nicotinic acid + N1-(5-Phospho-a-D-ribosyl)-5,6-dimethylbenzimidazoleNiacinamide + Water > Nicotinic acid + AmmoniaR01268NICOTINAMID-RXNNicotinamide ribotide + Pyrophosphate > Nicotinic acid + Phosphoribosyl pyrophosphateR01724NICOTINATEPRIBOSYLTRANS-RXNNicotinic acid + Water + Adenosine triphosphate + Phosphoribosyl pyrophosphate > Phosphate + Adenosine diphosphate + Pyrophosphate + nicotinate beta-D-ribonucleotide + ADP + Nicotinamide ribotidePW_R003016Dimethylbenzimidazole + nicotinate beta-D-ribonucleotide + Nicotinamide ribotide > Hydrogen ion + Nicotinic acid + N1-(5-Phospho-a-D-ribosyl)-5,6-dimethylbenzimidazolePW_R005142Nicotinamide ribotide + Pyrophosphate + Adenosine triphosphate + Water <> Nicotinic acid + Phosphoribosyl pyrophosphate + ADP + PhosphateNicotinamide ribotide + Pyrophosphate + Adenosine triphosphate + Water <> Nicotinic acid + Phosphoribosyl pyrophosphate + ADP + Phosphate