2.02012-05-31 10:24:20 -06002015-09-13 12:56:07 -0600ECMDB00232M2MDB000096Quinolinic acidQuinolinic acid is a dicarboxylic acid. It may be prepared by the oxidation of quinoline, either electrochemically, or with acidic hydrogen peroxide. (Wikipedia)2,3-Pyridinedicarboxylate2,3-Pyridinedicarboxylic acid3,4-Pyridinedicarboxylate3,4-Pyridinedicarboxylic acidPyridin-2,3-dicarbonsaeurePyridine-2,3-carboxylatePyridine-2,3-carboxylic acidPyridine-2,3-dicarboxylatePyridine-2,3-dicarboxylic acidPyridine-3,4-dicarboxylatePyridine-3,4-dicarboxylic acidQuinolinateQuinolinic acidC7H5NO4167.1189167.021857653pyridine-2,3-dicarboxylic acidquinolinic acid89-00-9OC(=O)C1=CC=CN=C1C(O)=OInChI=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-NSolidCytosollogp0.15logs-1.61solubility4.07e+00 g/lmelting_point190logp-1pka_strongest_acidic0.31pka_strongest_basic5.74iupacpyridine-2,3-dicarboxylic acidaverage_mass167.1189mono_mass167.021857653smilesOC(=O)C1=CC=CN=C1C(O)=OformulaC7H5NO4inchiInChI=1S/C7H5NO4/c9-6(10)4-2-1-3-8-5(4)7(11)12/h1-3H,(H,9,10)(H,11,12)inchikeyGJAWHXHKYYXBSV-UHFFFAOYSA-Npolar_surface_area87.49refractivity38.04polarizability14.34rotatable_bond_count2acceptor_count5donor_count2physiological_charge-2formal_charge0Tryptophan metabolismThe 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
PW000815ec00380MetabolicNicotinate and nicotinamide metabolismec00760beta-Alanine metabolismThe 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.PW000896ec00410MetabolicMetabolic pathwayseco01100NAD biosynthesisNicotinamide 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.
PW000829MetabolicNAD biosynthesis I (from aspartate)PYRIDNUCSYN-PWYSpecdb::CMs480Specdb::CMs481Specdb::CMs482Specdb::CMs3359Specdb::CMs29883Specdb::CMs29884Specdb::CMs30398Specdb::CMs30680Specdb::CMs30810Specdb::CMs31932Specdb::CMs32198Specdb::CMs37375Specdb::CMs135720Specdb::CMs143454Specdb::CMs1055112Specdb::CMs1055114Specdb::CMs1055116Specdb::CMs1055118Specdb::CMs1055120Specdb::NmrOneD1249Specdb::NmrOneD4684Specdb::NmrOneD4718Specdb::NmrOneD4719Specdb::NmrOneD143110Specdb::NmrOneD143111Specdb::NmrOneD143112Specdb::NmrOneD143113Specdb::NmrOneD143114Specdb::NmrOneD143115Specdb::NmrOneD143116Specdb::NmrOneD143117Specdb::NmrOneD143118Specdb::NmrOneD143119Specdb::NmrOneD143120Specdb::NmrOneD143121Specdb::NmrOneD143122Specdb::NmrOneD143123Specdb::NmrOneD143124Specdb::NmrOneD143125Specdb::NmrOneD143126Specdb::NmrOneD143127Specdb::NmrOneD143128Specdb::NmrOneD143129Specdb::MsMs388Specdb::MsMs389Specdb::MsMs390Specdb::MsMs3683Specdb::MsMs3684Specdb::MsMs3685Specdb::MsMs3686Specdb::MsMs3687Specdb::MsMs3688Specdb::MsMs3689Specdb::MsMs3690Specdb::MsMs3691Specdb::MsMs3692Specdb::MsMs20669Specdb::MsMs20670Specdb::MsMs20671Specdb::MsMs22220Specdb::MsMs22221Specdb::MsMs22222Specdb::MsMs437045Specdb::MsMs437046Specdb::MsMs438350Specdb::MsMs438351Specdb::MsMs438352Specdb::MsMs438353Specdb::NmrTwoD1003Specdb::NmrTwoD1226HMDB0023210661037C0372216675QUINOLINATENTMKeseler, I. 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M. Methods of preparation of quinolinic acid. Bashkirskii Khimicheskii Zhurnal (2001), 8(2), 9-14.http://hmdb.ca/system/metabolites/msds/000/000/168/original/HMDB00232.pdf?1358895529Quinolinate synthase AP11458NADA_ECOLInadAhttp://ecmdb.ca/proteins/P11458.xmlNicotinate-nucleotide pyrophosphorylase [carboxylating]P30011NADC_ECOLInadChttp://ecmdb.ca/proteins/P30011.xml2 Hydrogen ion + Phosphoribosyl pyrophosphate + Quinolinic acid <> Carbon dioxide + Nicotinamide ribotide + PyrophosphateR03348QUINOPRIBOTRANS-RXNDihydroxyacetone phosphate + Iminoaspartic acid <>2 Water + Phosphate + Quinolinic acidR04292QUINOLINATE-SYNTHA-RXNNicotinamide ribotide + Pyrophosphate + Carbon dioxide <> Quinolinic acid + Phosphoribosyl pyrophosphateR03348Quinolinic acid + 2 Water + Phosphate <> Iminoaspartic acid + Dihydroxyacetone phosphateR04292Iminoaspartic acid + Dihydroxyacetone phosphate > Quinolinic acid + Water + PhosphateQUINOLINATE-SYNTHA-RXNNicotinamide ribotide + Pyrophosphate + Carbon dioxide < Phosphoribosyl pyrophosphate + Quinolinic acid + Hydrogen ionQUINOPRIBOTRANS-RXNDihydroxyacetone phosphate + Iminoaspartic acid > Quinolinic acid +2 Water + Inorganic phosphateNicotinamide ribotide + Pyrophosphate + Carbon dioxide > Quinolinic acid + Phosphoribosyl pyrophosphateIminoaspartic acid + Dihydroxyacetone phosphate > Phosphate +2 Water + Quinolinic acidPW_R003008Quinolinic acid + Hydrogen ion + Phosphoribosyl pyrophosphate > Carbon dioxide + Pyrophosphate + nicotinate beta-D-ribonucleotide + Nicotinamide ribotidePW_R003009Dihydroxyacetone phosphate + Iminoaspartic acid <>2 Water + Phosphate + Quinolinic acidQuinolinic acid + 2 Water + Phosphate <> Iminoaspartic acid + Dihydroxyacetone phosphate2 Hydrogen ion + Phosphoribosyl pyrophosphate + Quinolinic acid <> Carbon dioxide + Nicotinamide ribotide + PyrophosphateDihydroxyacetone phosphate + Iminoaspartic acid <>2 Water + Phosphate + Quinolinic acid2 Hydrogen ion + Phosphoribosyl pyrophosphate + Quinolinic acid <> Carbon dioxide + Nicotinamide ribotide + PyrophosphateGutnick 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 glucoseShake flask and filter culture11.5uM0.037 oCK12 NCM3722Mid-Log Phase460000Bennett, 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 5:593-599.19561621Gutnick 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 glycerolShake flask and filter culture4.66uM0.037 oCK12 NCM3722Mid-Log Phase186400Bennett, 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 5:593-599.19561621Gutnick 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 acetateShake flask and filter culture0.9uM0.037 oCK12 NCM3722Mid-Log Phase36000Bennett, 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