2.0 2012-05-31 10:24:20 -0600 2015-09-13 12:56:07 -0600 ECMDB00232 M2MDB000096 Quinolinic acid Quinolinic acid is a dicarboxylic acid. It may be prepared by the oxidation of quinoline, either electrochemically, or with acidic hydrogen peroxide. (Wikipedia) 2,3-Pyridinedicarboxylate 2,3-Pyridinedicarboxylic acid 3,4-Pyridinedicarboxylate 3,4-Pyridinedicarboxylic acid Pyridin-2,3-dicarbonsaeure Pyridine-2,3-carboxylate Pyridine-2,3-carboxylic acid Pyridine-2,3-dicarboxylate Pyridine-2,3-dicarboxylic acid Pyridine-3,4-dicarboxylate Pyridine-3,4-dicarboxylic acid Quinolinate Quinolinic acid C7H5NO4 167.1189 167.021857653 pyridine-2,3-dicarboxylic acid quinolinic acid 89-00-9 OC(=O)C1=CC=CN=C1C(O)=O InChI=1S/C7H5NO4/c9-6(10)4-2-1-3-8-5(4)7(11)12/h1-3H,(H,9,10)(H,11,12) GJAWHXHKYYXBSV-UHFFFAOYSA-N Solid Cytosol logp 0.15 ALOGPS logs -1.61 ALOGPS solubility 4.07e+00 g/l ALOGPS melting_point 190 logp -1 ChemAxon pka_strongest_acidic 0.31 ChemAxon pka_strongest_basic 5.74 ChemAxon iupac pyridine-2,3-dicarboxylic acid ChemAxon average_mass 167.1189 ChemAxon mono_mass 167.021857653 ChemAxon smiles OC(=O)C1=CC=CN=C1C(O)=O ChemAxon formula C7H5NO4 ChemAxon inchi InChI=1S/C7H5NO4/c9-6(10)4-2-1-3-8-5(4)7(11)12/h1-3H,(H,9,10)(H,11,12) ChemAxon inchikey GJAWHXHKYYXBSV-UHFFFAOYSA-N ChemAxon polar_surface_area 87.49 ChemAxon refractivity 38.04 ChemAxon polarizability 14.34 ChemAxon rotatable_bond_count 2 ChemAxon acceptor_count 5 ChemAxon donor_count 2 ChemAxon physiological_charge -2 ChemAxon formal_charge 0 ChemAxon Tryptophan metabolism The biosynthesis of L-tryptophan begins with L-glutamine interacting with a chorismate through a anthranilate synthase which results in a L-glutamic acid, a pyruvic acid, a hydrogen ion and a 2-aminobenzoic acid. The aminobenzoic acid interacts with a phosphoribosyl pyrophosphate through an anthranilate synthase component II resulting in a pyrophosphate and a N-(5-phosphoribosyl)-anthranilate. The latter compound is then metabolized by an indole-3-glycerol phosphate synthase / phosphoribosylanthranilate isomerase resulting in a 1-(o-carboxyphenylamino)-1-deoxyribulose 5'-phosphate. This compound then interacts with a hydrogen ion through a indole-3-glycerol phosphate synthase / phosphoribosylanthranilate isomerase resulting in the release of carbon dioxide, a water molecule and a (1S,2R)-1-C-(indol-3-yl)glycerol 3-phosphate. The latter compound then interacts with a D-glyceraldehyde 3-phosphate and an Indole. The indole interacts with an L-serine through a tryptophan synthase, β subunit dimer resulting in a water molecule and an L-tryptophan. The metabolism of L-tryptophan starts with L-tryptophan being dehydrogenated by a tryptophanase / L-cysteine desulfhydrase resulting in the release of a hydrogen ion, an Indole and a 2-aminoacrylic acid. The latter compound is isomerized into a 2-iminopropanoate. This compound then interacts with a water molecule and a hydrogen ion spontaneously resulting in the release of an Ammonium and a pyruvic acid. The pyruvic acid then interacts with a coenzyme A through a NAD driven pyruvate dehydrogenase complex resulting in the release of a NADH, a carbon dioxide and an Acetyl-CoA PW000815 ec00380 Metabolic Nicotinate and nicotinamide metabolism ec00760 beta-Alanine metabolism The Beta-Alanine Metabolism starts with a product of Aspartate metabolism. Aspartate is decarboxylated by aspartate 1-decarboxylase, releasing carbon dioxide and Beta-alanine. Beta alanine is then metabolized through a pantothenate synthetase resulting in Pantothenic acid undergoes phosphorylation through a ATP driven pantothenate kinase, resulting in D-4-phosphopantothenate. Pantothenate (vitamin B5) is the universal precursor for the synthesis of the 4'-phosphopantetheine moiety of coenzyme A and acyl carrier protein. Only plants and microorganismscan synthesize pantothenate de novo - animals require a dietary supplement. The enzymes of this pathway are therefore considered to be antimicrobial drug targets. PW000896 ec00410 Metabolic 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 biosynthesis I (from aspartate) PYRIDNUCSYN-PWY Specdb::CMs 480 Specdb::CMs 481 Specdb::CMs 482 Specdb::CMs 3359 Specdb::CMs 29883 Specdb::CMs 29884 Specdb::CMs 30398 Specdb::CMs 30680 Specdb::CMs 30810 Specdb::CMs 31932 Specdb::CMs 32198 Specdb::CMs 37375 Specdb::CMs 135720 Specdb::CMs 143454 Specdb::CMs 1055112 Specdb::CMs 1055114 Specdb::CMs 1055116 Specdb::CMs 1055118 Specdb::CMs 1055120 Specdb::NmrOneD 1249 Specdb::NmrOneD 4684 Specdb::NmrOneD 4718 Specdb::NmrOneD 4719 Specdb::NmrOneD 143110 Specdb::NmrOneD 143111 Specdb::NmrOneD 143112 Specdb::NmrOneD 143113 Specdb::NmrOneD 143114 Specdb::NmrOneD 143115 Specdb::NmrOneD 143116 Specdb::NmrOneD 143117 Specdb::NmrOneD 143118 Specdb::NmrOneD 143119 Specdb::NmrOneD 143120 Specdb::NmrOneD 143121 Specdb::NmrOneD 143122 Specdb::NmrOneD 143123 Specdb::NmrOneD 143124 Specdb::NmrOneD 143125 Specdb::NmrOneD 143126 Specdb::NmrOneD 143127 Specdb::NmrOneD 143128 Specdb::NmrOneD 143129 Specdb::MsMs 388 Specdb::MsMs 389 Specdb::MsMs 390 Specdb::MsMs 3683 Specdb::MsMs 3684 Specdb::MsMs 3685 Specdb::MsMs 3686 Specdb::MsMs 3687 Specdb::MsMs 3688 Specdb::MsMs 3689 Specdb::MsMs 3690 Specdb::MsMs 3691 Specdb::MsMs 3692 Specdb::MsMs 20669 Specdb::MsMs 20670 Specdb::MsMs 20671 Specdb::MsMs 22220 Specdb::MsMs 22221 Specdb::MsMs 22222 Specdb::MsMs 437045 Specdb::MsMs 437046 Specdb::MsMs 438350 Specdb::MsMs 438351 Specdb::MsMs 438352 Specdb::MsMs 438353 Specdb::NmrTwoD 1003 Specdb::NmrTwoD 1226 HMDB00232 1066 1037 C03722 16675 QUINOLINATE NTM Keseler, I. 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Bashkirskii Khimicheskii Zhurnal (2001), 8(2), 9-14. http://hmdb.ca/system/metabolites/msds/000/000/168/original/HMDB00232.pdf?1358895529 Quinolinate synthase A P11458 NADA_ECOLI nadA http://ecmdb.ca/proteins/P11458.xml Nicotinate-nucleotide pyrophosphorylase [carboxylating] P30011 NADC_ECOLI nadC http://ecmdb.ca/proteins/P30011.xml 2 Hydrogen ion + Phosphoribosyl pyrophosphate + Quinolinic acid <> Carbon dioxide + Nicotinamide ribotide + Pyrophosphate R03348 QUINOPRIBOTRANS-RXN Dihydroxyacetone phosphate + Iminoaspartic acid <>2 Water + Phosphate + Quinolinic acid R04292 QUINOLINATE-SYNTHA-RXN Nicotinamide ribotide + Pyrophosphate + Carbon dioxide <> Quinolinic acid + Phosphoribosyl pyrophosphate R03348 Quinolinic acid + 2 Water + Phosphate <> Iminoaspartic acid + Dihydroxyacetone phosphate R04292 Iminoaspartic acid + Dihydroxyacetone phosphate > Quinolinic acid + Water + Phosphate QUINOLINATE-SYNTHA-RXN Nicotinamide ribotide + Pyrophosphate + Carbon dioxide < Phosphoribosyl pyrophosphate + Quinolinic acid + Hydrogen ion QUINOPRIBOTRANS-RXN Dihydroxyacetone phosphate + Iminoaspartic acid > Quinolinic acid +2 Water + Inorganic phosphate Nicotinamide ribotide + Pyrophosphate + Carbon dioxide > Quinolinic acid + Phosphoribosyl pyrophosphate Iminoaspartic acid + Dihydroxyacetone phosphate > Phosphate +2 Water + Quinolinic acid PW_R003008 Quinolinic acid + Hydrogen ion + Phosphoribosyl pyrophosphate > Carbon dioxide + Pyrophosphate + nicotinate beta-D-ribonucleotide + Nicotinamide ribotide PW_R003009 Dihydroxyacetone phosphate + Iminoaspartic acid <>2 Water + Phosphate + Quinolinic acid Quinolinic acid + 2 Water + Phosphate <> Iminoaspartic acid + Dihydroxyacetone phosphate 2 Hydrogen ion + Phosphoribosyl pyrophosphate + Quinolinic acid <> Carbon dioxide + Nicotinamide ribotide + Pyrophosphate Dihydroxyacetone phosphate + Iminoaspartic acid <>2 Water + Phosphate + Quinolinic acid 2 Hydrogen ion + Phosphoribosyl pyrophosphate + Quinolinic acid <> Carbon dioxide + Nicotinamide ribotide + Pyrophosphate Gutnick minimal complete medium (4.7 g/L KH2PO4; 13.5 g/L K2HPO4; 1 g/L K2SO4; 0.1 g/L MgSO4-7H2O; 10 mM NH4Cl) with 4 g/L glucose Shake flask and filter culture 11.5 uM 0.0 37 oC K12 NCM3722 Mid-Log Phase 46000 0 Bennett, B. D., Kimball, E. H., Gao, M., Osterhout, R., Van Dien, S. J., Rabinowitz, J. D. (2009). "Absolute metabolite concentrations and implied enzyme active site occupancy in Escherichia coli." Nat Chem Biol 5:593-599. 19561621 Gutnick minimal complete medium (4.7 g/L KH2PO4; 13.5 g/L K2HPO4; 1 g/L K2SO4; 0.1 g/L MgSO4-7H2O; 10 mM NH4Cl) with 4 g/L glycerol Shake flask and filter culture 4.66 uM 0.0 37 oC K12 NCM3722 Mid-Log Phase 18640 0 Bennett, B. D., Kimball, E. H., Gao, M., Osterhout, R., Van Dien, S. J., Rabinowitz, J. D. (2009). "Absolute metabolite concentrations and implied enzyme active site occupancy in Escherichia coli." Nat Chem Biol 5:593-599. 19561621 Gutnick minimal complete medium (4.7 g/L KH2PO4; 13.5 g/L K2HPO4; 1 g/L K2SO4; 0.1 g/L MgSO4-7H2O; 10 mM NH4Cl) with 4 g/L acetate Shake flask and filter culture 0.9 uM 0.0 37 oC K12 NCM3722 Mid-Log Phase 3600 0 Bennett, B. D., Kimball, E. H., Gao, M., Osterhout, R., Van Dien, S. J., Rabinowitz, J. D. (2009). "Absolute metabolite concentrations and implied enzyme active site occupancy in Escherichia coli." Nat Chem Biol 5:593-599. 19561621