2.0 2012-05-31 13:48:30 -0600 2015-09-13 12:56:10 -0600 ECMDB01259 M2MDB000313 Succinic acid semialdehyde Succinic acid semialdehyde is an intermediate in the catabolism of gamma-aminobutyrate (PMID 16435183). Succinate semialdehyde dehydrogenase is an enzyme that catalyses the reaction of succinate semialdehyde and NAD+ to form succinate and NADH. 2-Formylpropionate ethyl ester 2-Formylpropionic acid ethyl ester 3-Formylpropanoate 3-Formylpropanoic acid 4-Oxobutanoate 4-Oxobutanoic acid b-Formylpropionate b-Formylpropionic acid Beta-Formylpropionate Beta-Formylpropionic acid Butryaldehydate Butryaldehydic acid g-Oxybutyrate g-Oxybutyric acid Gamma-Oxybutyrate Gamma-Oxybutyric acid Succ-S-ald Succinaldehydate Succinaldehydic acid Succinate semialdehyde Succinic acid semialdehyde Succinic semialdehyde Succinyl semialdehyde β-Formylpropionate β-Formylpropionic acid γ-Oxybutyrate γ-Oxybutyric acid C4H6O3 102.0886 102.031694058 4-oxobutanoic acid succinic semialdehyde 692-29-5 OC(=O)CCC=O InChI=1S/C4H6O3/c5-3-1-2-4(6)7/h3H,1-2H2,(H,6,7) UIUJIQZEACWQSV-UHFFFAOYSA-N Solid Cytosol logp -0.47 ALOGPS logs 0.28 ALOGPS solubility 1.94e+02 g/l ALOGPS logp -0.56 ChemAxon pka_strongest_acidic 4.13 ChemAxon pka_strongest_basic -7 ChemAxon iupac 4-oxobutanoic acid ChemAxon average_mass 102.0886 ChemAxon mono_mass 102.031694058 ChemAxon smiles OC(=O)CCC=O ChemAxon formula C4H6O3 ChemAxon inchi InChI=1S/C4H6O3/c5-3-1-2-4(6)7/h3H,1-2H2,(H,6,7) ChemAxon inchikey UIUJIQZEACWQSV-UHFFFAOYSA-N ChemAxon polar_surface_area 54.37 ChemAxon refractivity 22.61 ChemAxon polarizability 9.26 ChemAxon rotatable_bond_count 3 ChemAxon acceptor_count 3 ChemAxon donor_count 1 ChemAxon physiological_charge -1 ChemAxon formal_charge 0 ChemAxon Butanoate metabolism ec00650 Alanine, aspartate and glutamate metabolism ec00250 Tyrosine metabolism ec00350 Vitamin B6 metabolism ec00750 Nicotinate and nicotinamide metabolism ec00760 beta-Alanine metabolism The Beta-Alanine Metabolism starts with a product of Aspartate metabolism. Aspartate is decarboxylated by aspartate 1-decarboxylase, releasing carbon dioxide and Beta-alanine. Beta alanine is then metabolized through a pantothenate synthetase resulting in Pantothenic acid undergoes phosphorylation through a ATP driven pantothenate kinase, resulting in D-4-phosphopantothenate. Pantothenate (vitamin B5) is the universal precursor for the synthesis of the 4'-phosphopantetheine moiety of coenzyme A and acyl carrier protein. Only plants and microorganismscan synthesize pantothenate de novo - animals require a dietary supplement. The enzymes of this pathway are therefore considered to be antimicrobial drug targets. PW000896 ec00410 Metabolic Propanoate metabolism Starting from L-threonine, this compound is deaminated through a threonine deaminase resulting in a hydrogen ion, a water molecule and a (2z)-2-aminobut-2-enoate. The latter compound then isomerizes to a 2-iminobutanoate, This compound then reacts spontaneously with hydrogen ion and a water molecule resulting in a ammonium and a 2-Ketobutyric acid. The latter compound interacts with CoA through a pyruvate formate-lyase / 2-ketobutyrate formate-lyase resulting in a formic acid and a propionyl-CoA. Propionyl-CoA can then be processed either into a 2-methylcitric acid or into a propanoyl phosphate. Propionyl-CoA interacts with oxalacetic acid and a water molecule through a 2-methylcitrate synthase resulting in a hydrogen ion, a CoA and a 2-Methylcitric acid.The latter compound is dehydrated through a 2-methylcitrate dehydratase resulting in a water molecule and cis-2-methylaconitate. The latter compound is then dehydrated by a bifunctional aconitate hydratase 2 and 2-methylisocitrate dehydratase resulting in a water molecule and methylisocitric acid. The latter compound is then processed by 2-methylisocitrate lyase resulting in a release of succinic acid and pyruvic acid. Succinic acid can then interact with a propionyl-CoA through a propionyl-CoA:succinate CoA transferase resulting in a propionic acid and a succinyl CoA. Succinyl-CoA is then isomerized through a methylmalonyl-CoA mutase resulting in a methylmalonyl-CoA. This compound is then decarboxylated through a methylmalonyl-CoA decarboxylase resulting in a release of Carbon dioxide and Propionyl-CoA. ropionyl-CoA interacts with a phosphate through a phosphate acetyltransferase / phosphate propionyltransferase resulting in a CoA and a propanoyl phosphate. Propionyl-CoA can react with a phosphate through a phosphate acetyltransferase / phosphate propionyltransferase resulting in a CoA and a propanoyl phosphate. The latter compound is then dephosphorylated through a ADP driven acetate kinase/propionate kinase protein complex resulting in an ATP and Propionic acid. Propionic acid can be processed by a reaction with CoA through a ATP-driven propionyl-CoA synthetase resulting in a pyrophosphate, an AMP and a propionyl-CoA. PW000940 ec00640 Metabolic Valine, leucine and isoleucine degradation ec00280 Microbial metabolism in diverse environments ec01120 Metabolic pathways eco01100 arginine metabolism The 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 cycle PW000790 Metabolic ornithine 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. PW000791 Metabolic 4-aminobutanoate degradation I E. coli can utilize putrescine as the sole source of carbon and nitrogen. The enzymes of the putrescine degradation II pathway are inducible by extracellular putrescine, leading to the production of GABA. Both enzymes of this pathway are inducible by putrescine in E. coli. This variant of the pathway includes a 2-oxoglutarate-dependent 4-aminobutyrate transaminase and an NAD+-dependent dehydrogenase. This combination of enzymes has been documented in bacteria and animals and in some plants. Regarding the hydrogenase, NAD-specific variants have been studied from many bacteria, plant and animals. PW002068 Metabolic 4-aminobutyrate degradation I PWY-6535 4-aminobutyrate degradation II PWY-6537 Specdb::CMs 950 Specdb::CMs 953 Specdb::CMs 2734 Specdb::CMs 31306 Specdb::CMs 31307 Specdb::CMs 32132 Specdb::CMs 32133 Specdb::CMs 37996 Specdb::CMs 156132 Specdb::NmrOneD 1672 Specdb::NmrOneD 147010 Specdb::NmrOneD 147011 Specdb::NmrOneD 147012 Specdb::NmrOneD 147013 Specdb::NmrOneD 147014 Specdb::NmrOneD 147015 Specdb::NmrOneD 147016 Specdb::NmrOneD 147017 Specdb::NmrOneD 147018 Specdb::NmrOneD 147019 Specdb::NmrOneD 147020 Specdb::NmrOneD 147021 Specdb::NmrOneD 147022 Specdb::NmrOneD 147023 Specdb::NmrOneD 147024 Specdb::NmrOneD 147025 Specdb::NmrOneD 147026 Specdb::NmrOneD 147027 Specdb::NmrOneD 147028 Specdb::NmrOneD 147029 Specdb::MsMs 1493 Specdb::MsMs 20750 Specdb::MsMs 20751 Specdb::MsMs 20752 Specdb::MsMs 22301 Specdb::MsMs 22302 Specdb::MsMs 22303 Specdb::MsMs 1471661 Specdb::MsMs 1471662 Specdb::MsMs 1471663 Specdb::MsMs 1471664 Specdb::MsMs 1471665 Specdb::MsMs 1471666 Specdb::MsMs 1471667 Specdb::MsMs 2233636 Specdb::MsMs 2275491 Specdb::MsMs 2275492 Specdb::MsMs 2275493 Specdb::MsMs 3093109 Specdb::MsMs 3093110 Specdb::MsMs 3093111 Specdb::NmrTwoD 1613 HMDB01259 1112 1080 C00232 16265 SUCC-S-ALD SSN Succinic 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 Struys, E. A., Jansen, E. E., Gibson, K. M., Jakobs, C. (2005). "Determination of the GABA analogue succinic semialdehyde in urine and cerebrospinal fluid by dinitrophenylhydrazine derivatization and liquid chromatography-tandem mass spectrometry: application to SSADH deficiency." J Inherit Metab Dis 28:913-920. 16435183 Yurtsever D. (2007). Fatty acid methyl ester profiling of Enterococcus and Esherichia coli for microbial source tracking. M.sc. Thesis. Villanova University: U.S.A Du L, Musson DG, Wang AQ: Stability studies of vorinostat and its two metabolites in human plasma, serum and urine. J Pharm Biomed Anal. 2006 Nov 16;42(5):556-64. Epub 2006 Jul 5. 16824724 Du L, Musson DG, Wang AQ: High turbulence liquid chromatography online extraction and tandem mass spectrometry for the simultaneous determination of suberoylanilide hydroxamic acid and its two metabolites in human serum. Rapid Commun Mass Spectrom. 2005;19(13):1779-87. 15945019 Hinshelwood A, McGarvie G, Ellis EM: Substrate specificity of mouse aldo-keto reductase AKR7A5. Chem Biol Interact. 2003 Feb 1;143-144:263-9. 12604212 Lee BC, Choe YS, Chi DY, Paik JY, Lee KH, Choi Y, Kim BT: 8-cyclopentadienyltricarbonyl 99mtc 8-oxooctanoic acid: a novel radiotracer for evaluation of medium chain fatty acid metabolism in the liver. Bioconjug Chem. 2004 Jan-Feb;15(1):121-7. 14733591 Parise RA, Holleran JL, Beumer JH, Ramalingam S, Egorin MJ: A liquid chromatography-electrospray ionization tandem mass spectrometric assay for quantitation of the histone deacetylase inhibitor, vorinostat (suberoylanilide hydroxamicacid, SAHA), and its metabolites in human serum. J Chromatogr B Analyt Technol Biomed Life Sci. 2006 Aug 18;840(2):108-15. Epub 2006 May 24. 16725386 Knerr I, Gibson KM, Jakobs C, Pearl PL: Neuropsychiatric morbidity in adolescent and adult succinic semialdehyde dehydrogenase deficiency patients. CNS Spectr. 2008 Jul;13(7):598-605. 18622364 Bruce, R.; Sims, K.; Pitts, F. N., Jr. Synthesis and purification of succinic semialdehyde. Analytical Biochemistry (1971), 41(1), 271-3. http://hmdb.ca/system/metabolites/msds/000/001/127/original/HMDB01259.pdf?1358461302 4-aminobutyrate aminotransferase P22256 GABT_ECOLI gabT http://ecmdb.ca/proteins/P22256.xml Succinate-semialdehyde dehydrogenase [NADP+] P25526 GABD_ECOLI gabD http://ecmdb.ca/proteins/P25526.xml 4-aminobutyrate aminotransferase_ P50457 PUUE_ECOLI puuE http://ecmdb.ca/proteins/P50457.xml Aldehyde dehydrogenase-like protein yneI P76149 YNEI_ECOLI yneI http://ecmdb.ca/proteins/P76149.xml Uncharacterized oxidoreductase yihU P0A9V8 YIHU_ECOLI yihU http://ecmdb.ca/proteins/P0A9V8.xml Water + NADP + Succinic acid semialdehyde >2 Hydrogen ion + NADPH + Succinic acid R00714 SUCCSEMIALDDEHYDROG-RXN gamma-Aminobutyric acid + alpha-Ketoglutarate <> L-Glutamate + Succinic acid semialdehyde R01648 Water + NAD + Succinic acid semialdehyde >2 Hydrogen ion + NADH + Succinic acid R00713 SUCCINATE-SEMIALDEHYDE-DEHYDROGENASE-RXN Hydrogen ion + NADH + Succinic acid semialdehyde <> gamma-Hydroxybutyrate + NAD 4-HYDROXYBUTYRATE-DEHYDROGENASE-RXN Succinic acid semialdehyde + NAD + Water <> Succinic acid + NADH + Hydrogen ion R00713 Succinic acid semialdehyde + NADP + Water <> Succinic acid + NADPH + Hydrogen ion R00714 NAD + gamma-Hydroxybutyrate <> Hydrogen ion + NADH + Succinic acid semialdehyde 4-HYDROXYBUTYRATE-DEHYDROGENASE-RXN Oxoglutaric acid + gamma-Aminobutyric acid <> L-Glutamate + Succinic acid semialdehyde GABATRANSAM-RXN Water + NAD + Succinic acid semialdehyde > Hydrogen ion + NADH + Succinic acid SUCCINATE-SEMIALDEHYDE-DEHYDROGENASE-RXN Succinic acid semialdehyde + NADP + Water > Succinic acid + NADPH + Hydrogen ion SUCCSEMIALDDEHYDROG-RXN Succinic acid semialdehyde + NADP + Water > Succinic acid + NADPH gamma-Aminobutyric acid + Oxoglutaric acid > Succinic acid semialdehyde + L-Glutamate GABATRANSAM-RXN Succinic acid semialdehyde + NAD(P)(+) + Water > Succinic acid + NAD(P)H Succinic acid semialdehyde + NAD + NADP + Water <> Succinic acid + NADH + NADPH +2 Hydrogen ion R00713 R00714 4-Hydroxybutanoic acid + NAD <> Succinic acid semialdehyde + NADH + Hydrogen ion R01644 gamma-Aminobutyric acid + Oxoglutaric acid > Succinic acid semialdehyde + L-Glutamic acid + L-Glutamate PW_R002691 Succinic acid semialdehyde + Water + NADP > NADPH +2 Hydrogen ion + Succinic acid + NADPH PW_R002692 Water + NADP + Succinic acid semialdehyde >2 Hydrogen ion + NADPH + Succinic acid gamma-Aminobutyric acid + alpha-Ketoglutarate <> L-Glutamate + Succinic acid semialdehyde gamma-Aminobutyric acid + alpha-Ketoglutarate <> L-Glutamate + Succinic acid semialdehyde