2.02012-05-31 13:58:41 -06002015-06-03 15:54:22 -0600ECMDB03357M2MDB000493N-AcetylornithineN-Acetylornithine is a intermediate in arginine and proline metabolism pathway. It is converted to ornithine via acetylornithine deacetylase (EC:3.5.1.16). (KEGG)(2S)-2-acetamido-5-aminopentanoate(2S)-2-acetamido-5-aminopentanoic acid<i>N</i>-α-acetylornithine<i>N</i>-acetylornithine<i>N<sup>2</sup></i>-acetyl-L-ornithine<i>N<sup>2</sup></i>-acetyl-ornithineAcetyl-OrnithineAcetylornithineAORN(2)-Acetyl-L-ornithinen-α-acetylornithineN-a-AcetylornithineN-AcOrnN-alpha-AcetylornithineN-α-AcetylornithineN2-Acetyl-L-ornithineN2-acetyl-ornithineC7H14N2O3174.1977174.100442324(2S)-5-amino-2-acetamidopentanoic acidN(2)-acetyl-L-ornithineCC(=O)N[C@@H](CCCN)C(O)=OInChI=1S/C7H14N2O3/c1-5(10)9-6(7(11)12)3-2-4-8/h6H,2-4,8H2,1H3,(H,9,10)(H,11,12)/t6-/m0/s1JRLGPAXAGHMNOL-LURJTMIESA-NSolidCytosollogp-2.73logs-0.66solubility3.78e+01 g/llogp-3.6pka_strongest_acidic3.82pka_strongest_basic9.9iupac(2S)-5-amino-2-acetamidopentanoic acidaverage_mass174.1977mono_mass174.100442324smilesCC(=O)N[C@@H](CCCN)C(O)=OformulaC7H14N2O3inchiInChI=1S/C7H14N2O3/c1-5(10)9-6(7(11)12)3-2-4-8/h6H,2-4,8H2,1H3,(H,9,10)(H,11,12)/t6-/m0/s1inchikeyJRLGPAXAGHMNOL-LURJTMIESA-Npolar_surface_area92.42refractivity42.65polarizability17.94rotatable_bond_count5acceptor_count4donor_count3physiological_charge0formal_charge0Arginine and proline metabolismec00330Lysine 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.PW000771ec00300MetabolicMetabolic pathwayseco01100arginine metabolismThe metabolism of L-arginine starts with the acetylation of L-glutamic acid resulting in a N-acetylglutamic acid while releasing a coenzyme A and a hydrogen ion. N-acetylglutamic acid is then phosphorylated via an ATP driven acetylglutamate kinase which yields a N-acetyl-L-glutamyl 5-phosphate. This compound undergoes a NDPH dependent reduction resulting in N-acetyl-L-glutamate 5-semialdehyde. This compound reacts with L-glutamic acid through a acetylornithine aminotransferase / N-succinyldiaminopimelate aminotransferase to produce a N-acetylornithine which is then deacetylated through a acetylornithine deacetylase which yield an ornithine.
L-glutamine is used to synthesize carbamoyl phosphate through the interaction of L-glutamine, water, ATP, and hydrogen carbonate. This reaction yields ADP, L-glutamic acid, phosphate, and hydrogen ion.
Carbamoyl phosphate and ornithine are used to catalyze the production of citrulline through an ornithine carbamoyltransferase. Citrulline reacts with L-aspartic acid through an ATP dependent enzyme, argininosuccinate synthase to produce pyrophosphate, AMP and argininosuccinic acid. Argininosussinic acid is then lyase to produce L-arginine and fumaric acid.
L-arginine can be metabolized into succinic acid by two different sets of reactions:
1. Arginine reacts with succinyl-CoA through a arginine N-succinyltransferase resulting in N2-succinyl-L-arginine while releasing CoA and Hydrogen Ion. N2-succinyl-L-arginine is then dihydrolase to produce a N2-succinyl-L-ornithine through a N-succinylarginine dihydrolase. This compound in turn reacts with oxoglutaric acid through succinylornithine transaminase resulting in L-glutamic acid and N2-succinyl-L-glutamic acid 5-semialdehyde. This compoud in turn reacts with a NAD dependent dehydrogenase resulting in N2-succinylglutamate while releasing NADH and hydrogen ion. N2-succinylglutamate reacts with water through a succinylglutamate desuccinylase resulting in L-glutamic acid and
a succinic acid. The succinic acid is then incorporated in the TCA cycle
2.Argine reacts with carbon dioxide and a hydrogen ion through a biodegradative arginine decarboxylase, resulting in Agmatine. This compound is then transformed into putrescine by reacting with water and an agmatinase, and releasing urea. Putrescine can be metabolized by reaction with either l-glutamic acid or oxoglutaric acid. If putrescine reacts with L-glutamic acid, it reacts through an ATP mediated gamma-glutamylputrescine producing a hydrogen ion, ADP, phosphate and gamma-glutamyl-L-putrescine. This compound is reduced by interacting with oxygen, water and a gamma-glutamylputrescine oxidoreductase resulting in ammonium, hydrogen peroxide and 4-gamma-glutamylamino butanal. This compound is dehydrogenated through a NADP mediated reaction lead by gamma-glutamyl-gamma-aminobutaryaldehyde dehydrogenase resulting in hydrogen ion, NADPH and 4-glutamylamino butanoate. In turn, the latter compound reacts with water through a gamma-glutamyl-gamma-aminobutyrate hydrolase resulting in L-glutamic acid and Gamma aminobutyric acid. On the other hand, if putrescine reacts with oxoglutaric acid through a putrescine aminotransferase, it results in L-glutamic acid, and a 4-aminobutyraldehyde. This compound reacts with water through a NAD dependent gamma aminobutyraldehyde dehydrogenase resulting in hydrogen ion, NADH and gamma-aminobutyric acid.
Gamma Aaminobutyric acid reacts with oxoglutaric acid through 4-aminobutyrate aminotransferase resulting in L-glutamic acid and succinic acid semialdehyde. This compound in turn can react with with either NADP or NAD to result in the production of succinic acid through succinate-semialdehyde dehydrogenase or aldehyde dehydrogenase-like protein yneI respectively. Succinic acid can then be integrated in the TCA cycle.
L-arginine is eventua lly metabolized into succinic acid which then goes to the TCA cyclePW000790Metabolicornithine metabolism
In the ornithine biosynthesis pathway of E. coli, L-glutamate is acetylated to N-acetylglutamate by the enzyme N-acetylglutamate synthase, encoded by the argA gene. The acetyl donor for this reaction is acetyl-CoA. N-acetylglutamic acid is then phosphorylated via an ATP driven acetylglutamate kinase which yields a N-acetyl-L-glutamyl 5-phosphate. This compound undergoes a NADPH dependent reduction resulting in N-acetyl-L-glutamate 5-semialdehyde. This compound reacts with L-glutamic acid through a acetylornithine aminotransferase / N-succinyldiaminopimelate aminotransferase to produce a N-acetylornithine which is then deacetylated through a acetylornithine deacetylase which yield an ornithine. Ornithine interacts with hydrogen ion through a Ornithine decarboxylase resulting in a carbon dioxide release and a putrescine
Putrescine can be metabolized by reaction with either l-glutamic acid or oxoglutaric acid. If putrescine reacts with L-glutamic acid, it reacts through an ATP mediated gamma-glutamylputrescine producing a hydrogen ion, ADP, phosphate and gamma-glutamyl-L-putrescine. This compound is reduced by interacting with oxygen, water and a gamma-glutamylputrescine oxidoreductase resulting in ammonium, hydrogen peroxide and 4-gamma-glutamylamino butanal. This compound is dehydrogenated through a NADP mediated reaction lead by gamma-glutamyl-gamma-aminobutaryaldehyde dehydrogenase resulting in hydrogen ion, NADPH and 4-glutamylamino butanoate. In turn, the latter compound reacts with water through a gamma-glutamyl-gamma-aminobutyrate hydrolase resulting in L-glutamic acid and Gamma aminobutyric acid. On the other hand, if putrescine reacts with oxoglutaric acid through a putrescine aminotransferase, it results in L-glutamic acid, and a 4-aminobutyraldehyde. This compound reacts with water through a NAD dependent gamma aminobutyraldehyde dehydrogenase resulting in hydrogen ion, NADH and gamma-aminobutyric acid.
Gamma Aaminobutyric acid reacts with oxoglutaric acid through 4-aminobutyrate aminotransferase resulting in L-glutamic acid and succinic acid semialdehyde. This compound in turn can react with with either NADP or NAD to result in the production of succinic acid through succinate-semialdehyde dehydrogenase or aldehyde dehydrogenase-like protein yneI respectively. Succinic acid can then be integrated in the TCA cycle.
PW000791Metabolicornithine biosynthesisGLUTORN-PWYSpecdb::CMs1611Specdb::CMs1721Specdb::CMs2560Specdb::CMs30113Specdb::CMs30114Specdb::CMs30652Specdb::CMs30653Specdb::CMs31456Specdb::CMs31457Specdb::CMs38583Specdb::CMs134858Specdb::CMs142592Specdb::NmrOneD4732Specdb::NmrOneD4733Specdb::NmrOneD135770Specdb::NmrOneD135771Specdb::NmrOneD135772Specdb::NmrOneD135773Specdb::NmrOneD135774Specdb::NmrOneD135775Specdb::NmrOneD135776Specdb::NmrOneD135777Specdb::NmrOneD135778Specdb::NmrOneD135779Specdb::NmrOneD135780Specdb::NmrOneD135781Specdb::NmrOneD135782Specdb::NmrOneD135783Specdb::NmrOneD135784Specdb::NmrOneD135785Specdb::NmrOneD135786Specdb::NmrOneD135787Specdb::NmrOneD135788Specdb::NmrOneD135789Specdb::MsMs28142Specdb::MsMs28143Specdb::MsMs28144Specdb::MsMs34700Specdb::MsMs34701Specdb::MsMs34702Specdb::MsMs437127Specdb::MsMs437128Specdb::MsMs437129Specdb::MsMs437130Specdb::MsMs437131Specdb::MsMs439178Specdb::MsMs445556Specdb::MsMs445557Specdb::MsMs445558Specdb::MsMs445559Specdb::MsMs445560Specdb::MsMs447330Specdb::MsMs448126Specdb::MsMs448127Specdb::MsMs2235701Specdb::MsMs2237654Specdb::MsMs2237865Specdb::MsMs2239721Specdb::MsMs2239860HMDB03357439232388369C0043716543N-ALPHA-ACETYLORNITHINEAORKeseler, I. 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Biochim Biophys Acta. 1979 Nov 1;587(4):638-42.508804Acetylornithine/succinyldiaminopimelate aminotransferaseP18335ARGD_ECOLIargDhttp://ecmdb.ca/proteins/P18335.xmlAcetylornithine deacetylaseP23908ARGE_ECOLIargEhttp://ecmdb.ca/proteins/P23908.xmlSuccinylornithine transaminaseP77581ASTC_ECOLIastChttp://ecmdb.ca/proteins/P77581.xmlN-Acetylornithine + alpha-Ketoglutarate <> N-Acetyl-L-glutamate 5-semialdehyde + L-GlutamateR02283N-Acetylornithine + Water <> Acetic acid + Ornithine + L-OrnithineR00669ACETYLORNDEACET-RXNN-Acetylornithine + Water <> Acetic acid + OrnithineR00669N-Acetylornithine + Water > Ornithine + Acetic acidACETYLORNDEACET-RXNN-Acetylornithine + Oxoglutaric acid < N-Acetyl-L-glutamate 5-semialdehyde + L-GlutamateACETYLORNTRANSAM-RXNN-Acetylornithine + Oxoglutaric acid > N-Acetyl-L-glutamate 5-semialdehyde + L-GlutamateN-acetyl-L-glutamate + L-Glutamic acid + L-Glutamate > Oxoglutaric acid + N-AcetylornithinePW_R002673N-Acetylornithine + Water > Acetic acid + L-Ornithine monochlorohydrate/ornithinePW_R002674N-Acetylornithine + Water > Ornithine + Acetic acid + OrnithinePW_R002694N-Acetyl-L-glutamate 5-semialdehyde + L-Glutamic acid + L-Glutamate > Oxoglutaric acid + N-AcetylornithinePW_R002675N-Acetylornithine + alpha-Ketoglutarate <> N-Acetyl-L-glutamate 5-semialdehyde + L-GlutamateN-Acetylornithine + Water <> Acetic acid + Ornithine + L-OrnithineN-Acetylornithine + Water <> Acetic acid + Ornithine + L-OrnithineGutnick 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 culture43.3uM0.037 oCK12 NCM3722Mid-Log Phase1732000Bennett, 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 culture398.0uM0.037 oCK12 NCM3722Mid-Log Phase15920000Bennett, 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 culture152.0uM0.037 oCK12 NCM3722Mid-Log Phase6080000Bennett, 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 5:593-599.1956162148 mM Na2HPO4, 22 mM KH2PO4, 10 mM NaCl, 45 mM (NH4)2SO4, supplemented with 1 mM MgSO4, 1 mg/l thiamine·HCl, 5.6 mg/l CaCl2, 8 mg/l FeCl3, 1 mg/l MnCl2·4H2O, 1.7 mg/l ZnCl2, 0.43 mg/l CuCl2·2H2O, 0.6 mg/l CoCl2·2H2O and 0.6 mg/l Na2MoO4·2H2O. 4 g/L GlucoBioreactor, pH controlled, O2 and CO2 controlled, dilution rate: 0.2/h14.1uM0.037 oCBW25113Stationary Phase, glucose limited564000Ishii, N., Nakahigashi, K., Baba, T., Robert, M., Soga, T., Kanai, A., Hirasawa, T., Naba, M., Hirai, K., Hoque, A., Ho, P. Y., Kakazu, Y., Sugawara, K., Igarashi, S., Harada, S., Masuda, T., Sugiyama, N., Togashi, T., Hasegawa, M., Takai, Y., Yugi, K., Arakawa, K., Iwata, N., Toya, Y., Nakayama, Y., Nishioka, T., Shimizu, K., Mori, H., Tomita, M. (2007). "Multiple high-throughput analyses monitor the response of E. coli to perturbations." Science 316:593-597.17379776Luria-Bertani (LB) mediaShake flask0.61uMtrue0.0337 oCBL21 DE3Stationary phase cultures (overnight culture)2427108Lin, Z., Johnson, L. C., Weissbach, H., Brot, N., Lively, M. O., Lowther, W. T. (2007). "Free methionine-(R)-sulfoxide reductase from Escherichia coli reveals a new GAF domain function." Proc Natl Acad Sci U S A 104:9597-9602.17535911