2.02012-05-31 10:24:10 -06002015-09-13 12:56:07 -0600ECMDB00225M2MDB000093Oxoadipic acid2-Oxoadipic acid is produced from lysine in the cytosol of cells via the saccharopine and the pipecolic acid pathways. Catabolites of hydroxylysine and tryptophan enter these pathways as 2-aminoadipic- -semialdehyde and 2-oxoadipate, respectively. In the cytoplasm, 2-oxoadipate is decarboxylated to glutaryl-CoA by the 2-oxoadipate dehydrogenase complex and then converted to acetyl-CoA.α-ketoadipateα-ketoadipic acid2-Keto-adipate2-Keto-adipic acid2-Ketoadipate2-Ketoadipic acid2-Oxo-hexanedioate2-Oxo-hexanedioic acid2-Oxoadipate2-Oxoadipic acid2-Oxohexanedioate2-Oxohexanedioic acid2-Oxohexanedionate2-Oxohexanedionic acidA-KetoadipateA-Ketoadipic acidA-OxoadipateA-Oxoadipic acidAlpha-KetoadipateAlpha-Ketoadipic acidAlpha-OxoadipateAlpha-Oxoadipic acidOxoadipateα-Ketoadipateα-Ketoadipic acidα-Oxoadipateα-Oxoadipic acidC6H8O5160.1247160.0371733662-oxohexanedioic acidoxoadipate3184-35-8OC(=O)CCCC(=O)C(O)=OInChI=1S/C6H8O5/c7-4(6(10)11)2-1-3-5(8)9/h1-3H2,(H,8,9)(H,10,11)FGSBNBBHOZHUBO-UHFFFAOYSA-NSolidOuter membraneInner membranelogp-0.37logs-0.83solubility2.34e+01 g/lmelting_point127logp0.34pka_strongest_acidic2.84pka_strongest_basic-9.7iupac2-oxohexanedioic acidaverage_mass160.1247mono_mass160.037173366smilesOC(=O)CCCC(=O)C(O)=OformulaC6H8O5inchiInChI=1S/C6H8O5/c7-4(6(10)11)2-1-3-5(8)9/h1-3H2,(H,8,9)(H,10,11)inchikeyFGSBNBBHOZHUBO-UHFFFAOYSA-Npolar_surface_area91.67refractivity33.48polarizability14.16rotatable_bond_count5acceptor_count5donor_count2physiological_charge-2formal_charge0Lysine biosynthesisLysine is biosynthesized from L-aspartic acid. L-aspartic acid can be incorporated into the cell through various methods: C4 dicarboxylate / orotate:H+ symporter ,
glutamate / aspartate : H+ symporter GltP, dicarboxylate transporter , C4 dicarboxylate / C4 monocarboxylate transporter DauA, glutamate / aspartate ABC transporter
L-aspartic acid is phosphorylated by an ATP-driven Aspartate kinase resulting in ADP and L-aspartyl-4-phosphate. L-aspartyl-4-phosphate is then dehydrogenated through an NADPH driven aspartate semialdehyde dehydrogenase resulting in a release of phosphate, NADP and L-aspartic 4-semialdehyde (involved in methionine biosynthesis).
L-aspartic 4-semialdehyde interacts with a pyruvic acid through a 4-hydroxy-tetrahydrodipicolinate synthase resulting in a release of hydrogen ion, water and
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate. The latter compound is then reduced by an NADPH driven 4-hydroxy-tetrahydrodipicolinate reductase resulting in a release of water, NADP and (S)-2,3,4,5-tetrahydrodipicolinate, This compound interacts with succinyl-CoA and water through a tetrahydrodipicolinate succinylase resulting in a release of coenzyme A and N-Succinyl-2-amino-6-ketopimelate. This compound interacts with L-glutamic acid through a N-succinyldiaminopimelate aminotransferase resulting in oxoglutaric acid, N-succinyl-L,L-2,6-diaminopimelate. The latter compound is then desuccinylated by reacting with water through a N-succinyl-L-diaminopimelate desuccinylase resulting in a succinic acid and L,L-diaminopimelate. This compound is then isomerized through a diaminopimelate epimerase resulting in a meso-diaminopimelate (involved in peptidoglyccan biosynthesis I). This compound is then decarboxylated by a diaminopimelate decarboxylase resulting in a release of carbon dioxide and L-lysine.
L-lysine is then incorporated into lysine degradation pathway. Lysine also regulate its own biosynthesis by repressing dihydrodipicolinate synthase and also repressing lysine-sensitive aspartokinase 3.
A metabolic connection joins synthesis of an amino acid, lysine, to synthesis of cell wall material. Diaminopimelate is a precursor both for lysine and for cell wall components. The synthesis of lysine, methionine and threonine share two reactions at the start of the three pathways, the reactions converting L-aspartate to L-aspartate semialdehyde. The reaction involving aspartate kinase is carried out by three isozymes, one specific for synthesis of each end product amino acid. Each of the three aspartate kinase isozymes is regulated by its corresponding end product amino acid.PW000771ec00300MetabolicTryptophan 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
PW000815ec00380MetabolicLysine degradationec00310Specdb::CMs3261Specdb::CMs31854Specdb::CMs31855Specdb::CMs31856Specdb::CMs31857Specdb::CMs37369Specdb::CMs99547Specdb::CMs99548Specdb::CMs99549Specdb::CMs99550Specdb::CMs136755Specdb::CMs144489Specdb::CMs1055083Specdb::CMs1055085Specdb::CMs1055087Specdb::CMs1055089Specdb::CMs1055090Specdb::CMs1055092Specdb::CMs1055094Specdb::CMs1055096Specdb::CMs1055098Specdb::CMs1055100Specdb::CMs1055102Specdb::NmrOneD1235Specdb::NmrOneD2333Specdb::NmrOneD3033Specdb::NmrOneD143070Specdb::NmrOneD143071Specdb::NmrOneD143072Specdb::NmrOneD143073Specdb::NmrOneD143074Specdb::NmrOneD143075Specdb::NmrOneD143076Specdb::NmrOneD143077Specdb::NmrOneD143078Specdb::NmrOneD143079Specdb::NmrOneD143080Specdb::NmrOneD143081Specdb::NmrOneD143082Specdb::NmrOneD143083Specdb::NmrOneD143084Specdb::NmrOneD143085Specdb::NmrOneD143086Specdb::NmrOneD143087Specdb::NmrOneD143088Specdb::NmrOneD143089Specdb::MsMs25874Specdb::MsMs25875Specdb::MsMs25876Specdb::MsMs32432Specdb::MsMs32433Specdb::MsMs32434Specdb::MsMs438012Specdb::MsMs438013Specdb::MsMs438014Specdb::MsMs438015Specdb::MsMs438016Specdb::MsMs440164Specdb::MsMs2226407Specdb::MsMs2228325Specdb::MsMs2228808Specdb::MsMs2230615Specdb::MsMs2233081Specdb::MsMs2233451Specdb::MsMs2235464Specdb::MsMs2770403Specdb::MsMs2770404Specdb::MsMs2770405Specdb::MsMs2908794Specdb::MsMs2908795Specdb::MsMs2908796Specdb::NmrTwoD1220HMDB002257170C00322157532K-ADIPATEKanehisa, 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 370:17-25.17765195Lee SH, Kim SO, Chung BC: Gas chromatographic-mass spectrometric determination of urinary oxoacids using O-(2,3,4,5,6-pentafluorobenzyl)oxime-trimethylsilyl ester derivatization and cation-exchange chromatography. J Chromatogr B Biomed Sci Appl. 1998 Nov 20;719(1-2):1-7.9869358Guneral F, Bachmann C: Age-related reference values for urinary organic acids in a healthy Turkish pediatric population. Clin Chem. 1994 Jun;40(6):862-6.8087979Fiermonte G, Dolce V, Palmieri L, Ventura M, Runswick MJ, Palmieri F, Walker JE: Identification of the human mitochondrial oxodicarboxylate carrier. Bacterial expression, reconstitution, functional characterization, tissue distribution, and chromosomal location. J Biol Chem. 2001 Mar 16;276(11):8225-30. Epub 2000 Nov 16.11083877Barshop BA, Nyhan WL, Naviaux RK, McGowan KA, Friedlander M, Haas RH: Kearns-Sayre syndrome presenting as 2-oxoadipic aciduria. Mol Genet Metab. 2000 Jan;69(1):64-8.10655159Schulze-Bergkamen A, Okun JG, Spiekerkotter U, Lindner M, Haas D, Kohlmuller D, Mayatepek E, Schulze-Bergkamen H, Greenberg CR, Zschocke J, Hoffmann GF, Kolker S: Quantitative acylcarnitine profiling in peripheral blood mononuclear cells using in vitro loading with palmitic and 2-oxoadipic acids: biochemical confirmation of fatty acid oxidation and organic acid disorders. Pediatr Res. 2005 Nov;58(5):873-80. Epub 2005 Sep 23.16183823Nelson, Randall B.; Gribble, Gordon W. Preparation of a-ketoadipic acid. Organic Preparations and Procedures International (1973), 5(2), 55-8.http://hmdb.ca/system/metabolites/msds/000/000/162/original/HMDB00225.pdf?13584627702-oxoglutarate dehydrogenase E1 componentP0AFG3ODO1_ECOLIsucAhttp://ecmdb.ca/proteins/P0AFG3.xmlOxoadipic acid + Coenzyme A + NAD <> Glutaryl-CoA + Carbon dioxide + NADH + Hydrogen ionR01933Oxoadipic acid + Enzyme N6-(lipoyl)lysine <> [Dihydrolipoyllysine-residue succinyltransferase] S-glutaryldihydrolipoyllysine + Carbon dioxideR01940Oxoadipic acid + Coenzyme A + NAD <> Glutaryl-CoA + Carbon dioxide + NADH + Hydrogen ion