2.0 2012-05-31 13:52:17 -0600 2015-06-03 15:54:06 -0600 ECMDB01418 M2MDB000380 O-Succinyl-L-homoserine O-succinyl-L-homoserine is a member of the chemical class known as Alpha Amino Acids and Derivatives. These are amino acids in which the amino group is attached to the carbon atom immediately adjacent to the carboxylate group (alpha carbon).O-succinyl-L-homoserine is involved in bacterial transfulfuration pathway. Cystathionine gamma-synthase (CGS) is a pyridoxal phosphate-dependent enzyme that catalyzes a gamma-replacement reaction, in which the succinyl group of an O-succinyl-L-homoserine (L-OSHS) is displaced by the thiol of L-cysteine to form L-cystathionine, in the first step of the bacterial transsulfuration pathway. Cystathionine gamma-synthase (CGS) is a pyridoxal phosphate-dependent enzyme that catalyzes a gamma-replacement reaction, in which the succinyl group of an O-succinyl-L-homoserine (L-OSHS) is displaced by the thiol of L-cysteine to form L-cystathionine, in the first step of the bacterial transsulfuration pathway. (PMID 14503880) (S)-Butanedioate mono(3-amino-3-carboxypropyl) ester (S)-Butanedioic acid mono(3-amino-3-carboxypropyl) ester Butanedioate mono(3-amino-3-carboxypropyl) ester Butanedioate mono[(3S)-3-amino-3-carboxypropyl] ester Butanedioic acid mono(3-amino-3-carboxypropyl) ester Butanedioic acid mono[(3S)-3-amino-3-carboxypropyl] ester L-2-Amino-4-hydroxy-Butyrate hydrogen succinate (ester) (8CI) L-2-Amino-4-hydroxy-Butyric acid hydrogen succinate (ester) (8CI) L-2-Amino-4-hydroxy-Butyric acid hydrogen succinic acid (ester) (8CI) L-Homoserine hydrogen butanedioate (ester) L-Homoserine hydrogen butanedioate (ester) (9CI) L-Homoserine hydrogen butanedioic acid (ester) L-Homoserine hydrogen butanedioic acid (ester) (9CI) O(4)-succinyl-L-homoserine O-4-Succinyl-L-homoserine O-Succinyl-homoserine O-Succinyl-L-homoserine O-Succinylhomoserine Succinate ester with 2-amino-4-hydroxybutyrate Succinate ester with 2-amino-4-hydroxybutyrate (7ci) Succinate ester with 2-amino-4-hydroxybutyric acid Succinate ester with 2-amino-4-hydroxybutyric acid (7CI) Succinate monoester with 2-amino-4-hydroxybutyrate Succinate monoester with 2-amino-4-hydroxybutyric acid Succinate monoester with L-2-amino-4-hydroxybutyrate Succinate monoester with L-2-amino-4-hydroxybutyrate (8ci) Succinate monoester with L-2-amino-4-hydroxybutyric acid Succinate monoester with L-2-amino-4-hydroxybutyric acid (8CI) Succinic acid ester with 2-amino-4-hydroxybutyric acid Succinic acid ester with 2-amino-4-hydroxybutyric acid (7CI) Succinic acid monoester with 2-amino-4-hydroxybutyric acid Succinic acid monoester with L-2-amino-4-hydroxybutyric acid Succinic acid monoester with L-2-amino-4-hydroxybutyric acid (8CI) Succinyl-homoserine SucHomoSer C8H13NO6 219.1919 219.074287153 (2S)-2-amino-4-[(3-carboxypropanoyl)oxy]butanoic acid O-succinyl-L-homoserine 1492-23-5 N[C@@H](CCOC(=O)CCC(O)=O)C(O)=O InChI=1S/C8H13NO6/c9-5(8(13)14)3-4-15-7(12)2-1-6(10)11/h5H,1-4,9H2,(H,10,11)(H,13,14)/t5-/m0/s1 GNISQJGXJIDKDJ-YFKPBYRVSA-N Cytosol logp -3.31 ALOGPS logs -1.40 ALOGPS solubility 8.69e+00 g/l ALOGPS logp -3.6 ChemAxon pka_strongest_acidic 1.69 ChemAxon pka_strongest_basic 9.46 ChemAxon iupac (2S)-2-amino-4-[(3-carboxypropanoyl)oxy]butanoic acid ChemAxon average_mass 219.1919 ChemAxon mono_mass 219.074287153 ChemAxon smiles N[C@@H](CCOC(=O)CCC(O)=O)C(O)=O ChemAxon formula C8H13NO6 ChemAxon inchi InChI=1S/C8H13NO6/c9-5(8(13)14)3-4-15-7(12)2-1-6(10)11/h5H,1-4,9H2,(H,10,11)(H,13,14)/t5-/m0/s1 ChemAxon inchikey GNISQJGXJIDKDJ-YFKPBYRVSA-N ChemAxon polar_surface_area 126.92 ChemAxon refractivity 46.95 ChemAxon polarizability 20.51 ChemAxon rotatable_bond_count 8 ChemAxon acceptor_count 6 ChemAxon donor_count 3 ChemAxon physiological_charge -1 ChemAxon formal_charge 0 ChemAxon Cysteine and methionine metabolism ec00270 Selenoamino acid metabolism ec00450 Sulfur metabolism The sulfur metabolism pathway starts in three possible ways. The first is the uptake of sulfate through an active transport reaction via a sulfate transport system containing an ATP-binding protein which hydrolyses ATP. Sulfate is converted by the sulfate adenylyltransferase enzymatic complex to adenosine phosphosulfate through the addition of adenine from a molecule of ATP, along with one phosphate group. Adenosine phosphosulfate is further converted to phoaphoadenosine phosphosulfate through an ATP hydrolysis and dehydrogenation reaction by the adenylyl-sulfate kinase. Phoaphoadenosine phosphosulfate is finally dehydrogenated and converted to sulfite by phosphoadenosine phosphosulfate reductase. This reaction requires magnesium, and adenosine 3',5'-diphosphate is the bi-product. A thioredoxin is also oxidized. Sulfite can also be produced from the dehydrogenation of cyanide along with the conversion of thiosulfate to thiocyanate by the thiosulfate sulfurtransferase enzymatic complex. Sulfite next undergoes a series of reactions that lead to the production of pyruvic acid, which is a precursor for pathways such as gluconeogenesis. The first reaction in this series is the conversion of sulfite to hydrogen sulfide through hygrogenation and the deoxygenation of sulfite to form a water molecule. The reaction is catalyzed by the sulfite reductase [NADPH] flavoprotein alpha and beta components. Siroheme, 4Fe-4S, flavin mononucleotide, and FAD function as cofactors or prosthetic groups. Hydrogen sulfide next undergoes dehydrogenation in a reversible reaction to form L-Cysteine and acetic acid, via the cysteine synthase complex and the coenzyme pyridoxal 5'-phosphate. L-Cysteine is dehydrogenated and converted to 2-aminoacrylic acid (a bronsted acid) and hydrogen sulfide(which may be reused) by a larger enzymatic complex composed of cysteine synthase A/B, protein malY, cystathionine-β-lyase, and tryptophanase, along with the coenzyme pyridoxal 5'-phosphate. 2-aminoacrylic acid isomerizes to 2-iminopropanoate, which along with a water molecule and a hydrogen ion is lastly converted to pyruvic acid and ammonium in a spontaneous fashion. The second possible initial starting point for sulfur metabolism is the import of taurine(an alternate sulfur source) into the cytoplasm via the taurine ABC transporter complex. Taurine, oxoglutaric acid, and oxygen are converted to sulfite by the alpha-ketoglutarate-dependent taurine dioxygenase. Carbon dioxide, succinic acid, and aminoacetaldehyde are bi-products of this reaction. Sulfite next enters pyruvic acid synthesis as already described. The third variant of sulfur metabolism starts with the import of an alkyl sulfate into the cytoplasm via an aliphatic sulfonate ABC transporter complex which hydrolyses ATP. The alkyl sulfate is dehydrogenated and along with oxygen is converted to sulfite and an aldehyde by the FMNH2-dependent alkanesulfonate monooxygenase enzyme. Water and flavin mononucleotide(which is used in a subsequent reaction as a prosthetic group) are also produced. Sulfite is next converted to pyruvic acid by the process already described. PW000922 ec00920 Metabolic Metabolic pathways eco01100 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 methionine biosynthesis I HOMOSER-METSYN-PWY Specdb::CMs 3191 Specdb::NmrOneD 4997 Specdb::NmrOneD 4998 Specdb::NmrOneD 327452 Specdb::NmrOneD 327453 Specdb::NmrOneD 327454 Specdb::NmrOneD 327455 Specdb::NmrOneD 327456 Specdb::NmrOneD 327457 Specdb::NmrOneD 327458 Specdb::NmrOneD 327459 Specdb::NmrOneD 327460 Specdb::NmrOneD 327461 Specdb::NmrOneD 327462 Specdb::NmrOneD 327463 Specdb::NmrOneD 327464 Specdb::NmrOneD 327465 Specdb::NmrOneD 327466 Specdb::NmrOneD 327467 Specdb::NmrOneD 327468 Specdb::NmrOneD 327469 Specdb::NmrOneD 327470 Specdb::NmrOneD 327471 Specdb::MsMs 25253 Specdb::MsMs 25254 Specdb::MsMs 25255 Specdb::MsMs 31811 Specdb::MsMs 31812 Specdb::MsMs 31813 439406 388523 C01118 16160 O-SUCCINYL-L-HOMOSERINE 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 Winder, C. L., Dunn, W. B., Schuler, S., Broadhurst, D., Jarvis, R., Stephens, G. M., Goodacre, R. (2008). 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Biochemistry 42:11297-11306. 14503880 Cystathionine gamma-synthase P00935 METB_ECOLI metB http://ecmdb.ca/proteins/P00935.xml Homoserine O-succinyltransferase P07623 META_ECOLI metA http://ecmdb.ca/proteins/P07623.xml L-Cysteine + O-Succinyl-L-homoserine <> L-Cystathionine + Hydrogen ion + Succinic acid R03260 O-SUCCHOMOSERLYASE-RXN L-Homoserine + Succinyl-CoA <> Coenzyme A + O-Succinyl-L-homoserine R01777 HOMSUCTRAN-RXN O-Succinyl-L-homoserine + Water <> 2-Ketobutyric acid + Succinic acid + Ammonia R00999 O-Succinyl-L-homoserine + Hydrogen sulfide <> L-Homocysteine + Succinic acid R01288 Cystathionine + Succinic acid <> O-Succinyl-L-homoserine + L-Cysteine R02508 O-Succinyl-L-homoserine + L-Cysteine <> L-Cystathionine + Succinic acid R03260 O-Succinyl-L-homoserine + Selenocysteine <> Selenocystathionine + Succinic acid R04946 L-Homoserine + Succinyl-CoA > O-Succinyl-L-homoserine + Coenzyme A HOMSUCTRAN-RXN Hydrogen ion + 2-Ketobutyric acid + Succinic acid + Ammonia O-Succinyl-L-homoserine + Water R00999 METBALT-RXN L-Cysteine + O-Succinyl-L-homoserine > Hydrogen ion + Succinic acid + L-Cystathionine O-SUCCHOMOSERLYASE-RXN Succinyl-CoA + L-Homoserine > CoA + O-Succinyl-L-homoserine O-Succinyl-L-homoserine + L-Cysteine > L-Cystathionine + Succinic acid L-Homoserine + Succinyl-CoA + L-Homoserine + Succinyl-CoA > Coenzyme A + O-Succinyl-L-homoserine PW_R002889