2.0 2012-05-31 14:21:18 -0600 2015-06-03 17:19:03 -0600 ECMDB12249 M2MDB000833 L-Aspartate-semialdehyde L-Aspartate-semialdehyde is involved in both the lysine biosynthesis and homoserine biosynthesis pathways. AspSA L-aspartate &beta;-semialdehyde L-Aspartate 4-semialdehyde L-aspartate b-semialdehyde L-Aspartate beta-semialdehyde L-Aspartate β-semialdehyde L-Aspartate-4-semialdehyde L-Aspartic 4-semialdehyde L-Aspartic acid &beta;-semialdehyde L-Aspartic acid 4-semialdehyde L-Aspartic acid b-semialdehyde L-Aspartic acid beta-semialdehyde L-Aspartic acid β-semialdehyde L-Aspartic acid-4-semialdehyde L-Aspartic acid-semialdehyde C4H7NO3 117.1033 117.042593095 (2S)-2-amino-4-oxobutanoic acid L-aspartic 4-semialdehyde 15106-57-7 N[C@@H](CC=O)C(O)=O InChI=1S/C4H7NO3/c5-3(1-2-6)4(7)8/h2-3H,1,5H2,(H,7,8)/t3-/m0/s1 HOSWPDPVFBCLSY-VKHMYHEASA-N Solid Cytosol logp -2.73 ALOGPS logs 0.28 ALOGPS solubility 2.25e+02 g/l ALOGPS logp -3.6 ChemAxon pka_strongest_acidic 1.95 ChemAxon pka_strongest_basic 8.98 ChemAxon iupac (2S)-2-amino-4-oxobutanoic acid ChemAxon average_mass 117.1033 ChemAxon mono_mass 117.042593095 ChemAxon smiles N[C@@H](CC=O)C(O)=O ChemAxon formula C4H7NO3 ChemAxon inchi InChI=1S/C4H7NO3/c5-3(1-2-6)4(7)8/h2-3H,1,5H2,(H,7,8)/t3-/m0/s1 ChemAxon inchikey HOSWPDPVFBCLSY-VKHMYHEASA-N ChemAxon polar_surface_area 80.39 ChemAxon refractivity 25.61 ChemAxon polarizability 10.51 ChemAxon rotatable_bond_count 3 ChemAxon acceptor_count 4 ChemAxon donor_count 2 ChemAxon physiological_charge 0 ChemAxon formal_charge 0 ChemAxon Arginine and proline metabolism ec00330 Cysteine and methionine metabolism ec00270 Phenylalanine, tyrosine and tryptophan biosynthesis ec00400 Glycine, serine and threonine metabolism ec00260 Lysine biosynthesis Lysine 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. PW000771 ec00300 Metabolic Microbial metabolism in diverse environments ec01120 Monobactam biosynthesis eco00261 Metabolic pathways eco01100 Secondary Metabolites: threonine biosynthesis from aspartate The biosynthesis of threonine starts with L-aspartic acid being phosphorylated by an ATP driven Aspartate kinase resulting in an a release of an ADP and an L-aspartyl-4-phosphate. This compound interacts with a hydrogen ion through an NADPH driven aspartate semialdehyde dehydrogenase resulting in the release of a phosphate, an NADP and a L-aspartate-semialdehyde.The latter compound interacts with a hydrogen ion through a NADPH driven aspartate kinase / homoserine dehydrogenase resulting in the release of an NADP and a L-homoserine. L-homoserine is phosphorylated through an ATP driven homoserine kinase resulting in the release of an ADP, a hydrogen ion and a O-phosphohomoserine. The latter compound then interacts with a water molecule threonine synthase resulting in the release of a phosphate and an L-threonine. PW000976 Metabolic methionine biosynthesis The de novo biosynthesis of methionine is an energy-costly process involving inputs from several other pathways. The carbon skeleton of methionine is derived from aspartate. The sulfur is derived from cysteine which derives its sulfur from sulfate assimilation. The methyl group is derived from serine via one-carbon metabolism. Methionine is also converted to S-adenosyl-L-methionine, a methyl group donor, by the product of gene metK . The synthesis starts with a product of the lysine biosynthesis pathway, L-aspartate-semialdehyde. This compound is dehydrogenated by a NADPH aspartate kinase / homoserine dehydrogenase resulting in NADP and L-homoserine. Homoserine is activated by O-succinylation in a reaction catalyzed by MetA. The product O-succinyl-L-homoserine combines with cysteine to form cystathionine in a reaction catalyzed by MetB. Lyase cleavage of cystathionine by MetC forms homocysteine. This β-cystathionase activity can also be supplied by MalY as demonstrated in vivo by the ability of constitutive MalY expression to complement metC mutants auxotrophic for methionine . Homocysteine is subsequently methylated by either MetH or MetE to produce methionine. In E. coli MetH can function only in the presence of exogenously supplied vitamin B12 (cobalamin), which represses MetE expression. B12 is likely to be available in the gut. In the absence of exogenously supplied B12, MetE catalyzes this final step of de novo methionine biosynthesis. L-methionine is then transferred into the periplasmic space through a leucine efflux transporter. Under stressful conditions there is further regulation of the pathway enzymes. Under heat-shock conditions growth is slowed due to the thermal instability of MetA. Oxidative stress affects MetE which contains an oxidation-sensitive cysteine residue at position 645 near the active site. Oxidation of methionone itself can also occur although the cell contains methionine sufloxide reductases MsrA and MsrB to combat this. Weak organic acids also generate oxidative stress, with more complex effects. Sulfur limitation depletes homocysteine which serves as a coactivator for MetR activation of MetE expression. Due to the absence of this pathway in mammals, some of the bacterial biosynthetic enzymes are potential drug targets. In addition, although methionine is used as a food additive and a medication, its industrial scale production in microorganisms has not yet been achieved due to the complexity and strong regulation of its biosynthetic pathway. PW000814 Metabolic threonine biosynthesis The biosynthesis of threonine starts with oxalacetic acid interacting with an L-glutamic acid through an aspartate aminotransferase resulting in a oxoglutaric acid and an L-aspartic acid. The latter compound is then phosphorylated by an ATP driven Aspartate kinase resulting in an a release of an ADP and an L-aspartyl-4-phosphate. This compound interacts with a hydrogen ion through an NADPH driven aspartate semialdehyde dehydrogenase resulting in the release of a phosphate, an NADP and a L-aspartate-semialdehyde.The latter compound interacts with a hydrogen ion through a NADPH driven aspartate kinase / homoserine dehydrogenase resulting in the release of an NADP and a L-homoserine. L-homoserine is phosphorylated through an ATP driven homoserine kinase resulting in the release of an ADP, a hydrogen ion and a O-phosphohomoserine. The latter compound then interacts with a water molecule threonine synthase resulting in the release of a phosphate and an L-threonine. PW000817 Metabolic lysine biosynthesis I DAPLYSINESYN-PWY homoserine biosynthesis HOMOSERSYN-PWY Specdb::CMs 2469 Specdb::CMs 39884 Specdb::CMs 160410 Specdb::NmrOneD 96638 Specdb::NmrOneD 96639 Specdb::NmrOneD 96640 Specdb::NmrOneD 96641 Specdb::NmrOneD 96642 Specdb::NmrOneD 96643 Specdb::NmrOneD 96644 Specdb::NmrOneD 96645 Specdb::NmrOneD 96646 Specdb::NmrOneD 96647 Specdb::NmrOneD 96648 Specdb::NmrOneD 96649 Specdb::NmrOneD 96650 Specdb::NmrOneD 96651 Specdb::NmrOneD 96652 Specdb::NmrOneD 96653 Specdb::NmrOneD 96654 Specdb::NmrOneD 96655 Specdb::NmrOneD 96656 Specdb::NmrOneD 96657 Specdb::MsMs 25334 Specdb::MsMs 25335 Specdb::MsMs 25336 Specdb::MsMs 31892 Specdb::MsMs 31893 Specdb::MsMs 31894 Specdb::MsMs 2817669 Specdb::MsMs 2817670 Specdb::MsMs 2817671 Specdb::MsMs 2887328 Specdb::MsMs 2887329 Specdb::MsMs 2887330 HMDB12249 439235 388372 C00441 L-ASPARTATE-SEMIALDEHYDE Keseler, 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. 21097882 Kanehisa, 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. 22080510 van 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. 17765195 Bifunctional aspartokinase/homoserine dehydrogenase 1 P00561 AK1H_ECOLI thrA http://ecmdb.ca/proteins/P00561.xml Bifunctional aspartokinase/homoserine dehydrogenase 2 P00562 AK2H_ECOLI metL http://ecmdb.ca/proteins/P00562.xml Dihydrodipicolinate synthase P0A6L2 DAPA_ECOLI dapA http://ecmdb.ca/proteins/P0A6L2.xml Aspartate-semialdehyde dehydrogenase P0A9Q9 DHAS_ECOLI asd http://ecmdb.ca/proteins/P0A9Q9.xml Uncharacterized protein yjhH P39359 YJHH_ECOLI yjhH http://ecmdb.ca/proteins/P39359.xml Uncharacterized protein yagE P75682 YAGE_ECOLI yagE http://ecmdb.ca/proteins/P75682.xml L-Homoserine + NADP <> L-Aspartate-semialdehyde + Hydrogen ion + NADPH R01775 L-Aspartate-semialdehyde + Pyruvic acid > 2,3-Dihydrodipicolinic acid + Hydrogen ion +2 Water R02292 DIHYDRODIPICSYN-RXN L-Aspartate-semialdehyde + NADP + Phosphate <> L-Aspartyl-4-phosphate + Hydrogen ion + NADPH R02291 ASPARTATE-SEMIALDEHYDE-DEHYDROGENASE-RXN L-Homoserine + NAD <> L-Aspartate-semialdehyde + NADH + Hydrogen ion R01773 L-Aspartate-semialdehyde + Pyruvic acid <> 2,3-Dihydrodipicolinic acid +2 Water R02292 Pyruvic acid + L-Aspartate-semialdehyde <> Hydrogen ion + Water + 2,3-Dihydrodipicolinic acid DIHYDRODIPICSYN-RXN NAD(P)⁺ + L-Homoserine < NAD(P)H + L-Aspartate-semialdehyde + Hydrogen ion HOMOSERDEHYDROG-RXN L-Homoserine + NAD(P)(+) > L-Aspartate-semialdehyde + NAD(P)H L-Aspartate-semialdehyde + Pyruvic acid > (S)-2,3-dihydrodipicolinate +2 Water L-Aspartate-semialdehyde + Inorganic phosphate + NADP > L-4-aspartyl phosphate + NADPH Pyruvic acid + L-Aspartate-semialdehyde <> (2S,4S)-4-Hydroxy-2,3,4,5-tetrahydrodipicolinate + Water R10147 L-Aspartyl-4-phosphate + NADPH + Hydrogen ion + NADPH > Phosphate + NADP + L-Aspartate-semialdehyde PW_R002526 L-Aspartate-semialdehyde + Pyruvic acid > Hydrogen ion + Water + (2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate + (2S,4S)-4-Hydroxy-2,3,4,5-tetrahydrodipicolinate PW_R002527 L-Aspartate-semialdehyde + Hydrogen ion + NADPH + NADPH > NADP + L-Homoserine + L-Homoserine PW_R002918 L-Aspartate-semialdehyde + Pyruvic acid >2 2,3-Dihydrodipicolinic acid + Hydrogen ion +2 Water L-Aspartate-semialdehyde + NADP + Phosphate <> L-Aspartyl-4-phosphate + Hydrogen ion + NADPH L-Aspartate-semialdehyde + Pyruvic acid >2 2,3-Dihydrodipicolinic acid + Hydrogen ion +2 Water