2.02012-05-31 14:26:38 -06002015-09-17 15:41:54 -0600ECMDB20085M2MDB0009334-Amino-4-deoxychorismate4-amino-4-deoxychorismate (or ADC) can be classified as a member of the Dicarboxylic Acids and Derivatives. These are organic compounds containing exactly two carboxylic acid groups. ADC is involved in antibiotic biosynthesis. In some antibiotic producers, p-aminobenzoic acid (PABA) or its immediate precursor, 4-amino-4-deoxychorismate (ADC), is involved in primary metabolism and antibiotic biosynthesis. (PMID 19389784) In Escherichia coli, the production of PABA is catalyzed by the PabC protein, a beta-lyase that converts 4-amino-4-deoxychorismate (ADC)--the reaction product of the PabA and PabB enzymes--to PABA and pyruvate. (PMID 15500462) 4-Amino-4-deoxychorismate lyase (ADCL) is a member of the fold-type IV of PLP dependent enzymes that converts 4-amino-4-deoxychorismate (ADC) to p-aminobenzoate and pyruvate. (PMID 10876155)4-Amino-4-deoxychorismic acidADCADCAC10H10NO5224.193224.056446006(3R,4R)-4-amino-3-[(1-carboxyeth-1-en-1-yl)oxy]cyclohexa-1,5-diene-1-carboxylic acid4-amino-4-deoxychorismic acid133442-18-9[H][C@@]1(N)C=CC(=C[C@@]1([H])OC(=C)C([O-])=O)C(O)=OInChI=1S/C10H11NO5/c1-5(9(12)13)16-8-4-6(10(14)15)2-3-7(8)11/h2-4,7-8H,1,11H2,(H,12,13)(H,14,15)/p-1/t7-,8-/m1/s1OIUJHGOLFKDBSU-HTQZYQBOSA-MCytosollogp-2.33logs-1.29solubility1.16e+01 g/llogp-2.8pka_strongest_acidic3.24pka_strongest_basic9.12iupac(3R,4R)-4-amino-3-[(1-carboxyeth-1-en-1-yl)oxy]cyclohexa-1,5-diene-1-carboxylic acidaverage_mass224.193mono_mass224.056446006smiles[H][C@@]1(N)C=CC(=C[C@@]1([H])OC(=C)C([O-])=O)C(O)=OformulaC10H10NO5inchiInChI=1S/C10H11NO5/c1-5(9(12)13)16-8-4-6(10(14)15)2-3-7(8)11/h2-4,7-8H,1,11H2,(H,12,13)(H,14,15)/p-1/t7-,8-/m1/s1inchikeyOIUJHGOLFKDBSU-HTQZYQBOSA-Mpolar_surface_area109.85refractivity55.97polarizability20.91rotatable_bond_count4acceptor_count6donor_count3physiological_charge-1formal_charge0Folate biosynthesisThe biosynthesis of folic acid begins with a product of purine nucleotides de novo biosynthesis pathway, GTP. This compound is involved in a reaction with water through a GTP cyclohydrolase 1 protein complex, resulting in a hydrogen ion, formic acid and 7,8-dihydroneopterin 3-triphosphate. The latter compound is dephosphatased through a dihydroneopterin triphosphate pyrophosphohydrolase resulting in the release of a pyrophosphate, hydrogen ion and 7,8-dihydroneopterin 3-phosphate. The latter compound reacts with water spontaneously resulting in the release of a phosphate and a 7,8 -dihydroneopterin. This compound reacts with a dihydroneopterin aldolase, releasing a glycoaldehyde and 6-hydroxymethyl-7,9-dihydropterin. The latter compound is phosphorylated with a ATP-driven 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase resulting in a (2-amino-4-hydroxy-7,8-dihydropteridin-6-yl)methyl diphosphate.
Chorismate is metabolized by reacting with L-glutamine through a 4-amino-4-deoxychorismate synthase resulting in L-glutamic acid and 4-amino-4-deoxychorismate. The latter compound then reacts through an aminodeoxychorismate lyase resulting in pyruvic acid,hydrogen ion and p-aminobenzoic acid.
(2-amino-4-hydroxy-7,8-dihydropteridin-6-yl)methyl diphosphate and p-aminobenzoic acid react through a dihydropteroate synthase resulting in pyrophosphate and 7,8-dihydropteroic acid. This compound reacts with L-glutamic acid through an ATP driven bifunctional folylpolyglutamate synthetase / dihydrofolate synthetase resulting in a 7,8-dihydrofolate monoglutamate. This compound is reduced through an NADPH mediated dihydrofolate reductase resulting in a tetrahydrofate.
This product goes on to a one carbon pool by folate pathway.
PW000908ec00790Metabolic<i>p</i>-aminobenzoate biosynthesisPWY-6543Specdb::CMs2729Specdb::NmrOneD247848Specdb::NmrOneD247849Specdb::NmrOneD247850Specdb::NmrOneD247851Specdb::NmrOneD247852Specdb::NmrOneD247853Specdb::NmrOneD247854Specdb::NmrOneD247855Specdb::NmrOneD247856Specdb::NmrOneD247857Specdb::NmrOneD247858Specdb::NmrOneD247859Specdb::NmrOneD247860Specdb::NmrOneD247861Specdb::NmrOneD247862Specdb::NmrOneD247863Specdb::NmrOneD247864Specdb::NmrOneD247865Specdb::NmrOneD247866Specdb::NmrOneD247867Specdb::MsMs24866Specdb::MsMs24867Specdb::MsMs24868Specdb::MsMs31424Specdb::MsMs31425Specdb::MsMs31426Specdb::MsMs3608122Specdb::MsMs3608123Specdb::MsMs3608124Specdb::MsMs3608125Specdb::MsMs3608126Specdb::MsMs3608127443142391414C11355351814-AMINO-4-DEOXYCHORISMATEKeseler, 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 80:2939-2948.18331064Zhang, Y., Bai, L., Deng, Z. (2009). "Functional characterization of the first two actinomycete 4-amino-4-deoxychorismate lyase genes." Microbiology 155:2450-2459.19389784Basset, G. J., Ravanel, S., Quinlivan, E. P., White, R., Giovannoni, J. J., Rebeille, F., Nichols, B. P., Shinozaki, K., Seki, M., Gregory, J. F. 3rd, Hanson, A. D. (2004). "Folate synthesis in plants: the last step of the p-aminobenzoate branch is catalyzed by a plastidial aminodeoxychorismate lyase." Plant J 40:453-461.15500462Para-aminobenzoate synthase glutamine amidotransferase component IIP00903PABA_ECOLIpabAhttp://ecmdb.ca/proteins/P00903.xmlPara-aminobenzoate synthase component 1P05041PABB_ECOLIpabBhttp://ecmdb.ca/proteins/P05041.xmlAminodeoxychorismate lyaseP28305PABC_ECOLIpabChttp://ecmdb.ca/proteins/P28305.xmlChorismate + L-Glutamine <> 4-Amino-4-deoxychorismate + L-GlutamateR01716PABASYN-RXN4-Amino-4-deoxychorismate <> p-Aminobenzoic acid + Hydrogen ion + Pyruvic acidR05553ADCLY-RXN4-Amino-4-deoxychorismate <> p-Aminobenzoic acid + Pyruvic acidR05553Chorismate + L-Glutamine > 4-Amino-4-deoxychorismate + L-Glutamate4-Amino-4-deoxychorismate > p-Aminobenzoic acid + Pyruvic acid4-amino-4-deoxychorismate + 4-Amino-4-deoxychorismate > Pyruvic acid + Hydrogen ion + p-Aminobenzoic acidPW_R003402Chorismate + L-Glutamine > L-Glutamic acid + 4-amino-4-deoxychorismate + L-Glutamate + 4-Amino-4-deoxychorismatePW_R003403Chorismate + L-Glutamine <>4 4-Amino-4-deoxychorismate + L-Glutamate4 4-Amino-4-deoxychorismate <> p-Aminobenzoic acid + Hydrogen ion + Pyruvic acidChorismate + L-Glutamine <>4 4-Amino-4-deoxychorismate + L-Glutamate