2.02012-05-31 14:20:49 -06002015-06-03 17:19:02 -0600ECMDB12161M2MDB0008244-(Glutamylamino) butanoate4-(Glutamylamino) butanoate is a polyamine that is an intermediate in putrescine degradation . Polyamines (the most common of which are putrescine , spermidine , and spermine ), a group of positively charged small molecules present in virtually all living organisms, have been implicated in many biological processes, including binding to nucleic acids, stabilizing membranes, and stimulating several enzymes. Although polyamines are clearly necessary for optimal cell growth, a surplus of polyamines can cause inhibition of growth and protein synthesis, and thus a balance is desired between the production and breakdown of polyamines. In putrescine degradation , 4-(Glutamylamino) butanoate is a substrate for gamma-glutamyl-gamma-aminobutyrate hydrolase (puuD) and can be generated from the hydrolysis of gamma-glutamyl-gamma-aminobutyraldehyde.γ-glu-GABAγ-glutamyl-γ-aminobutanoateγ-glutamyl-γ-aminobutanoic acidγ-glutamyl-γ-aminobutyrateγ-glutamyl-γ-aminobutyric acid4-(Glutamylamino) butanoic acid4-(Glutamylamino)butanoate4-(Glutamylamino)butanoic acid4-(L-g-glutamylamino)Butanoate4-(L-g-glutamylamino)Butanoic acid4-(L-gamma-Glutamylamino)butanoate4-(L-gamma-Glutamylamino)butanoic acid4-(L-Glutam-5-ylamino)butanoate4-(L-Glutam-5-ylamino)butanoic acid4-(L-γ-glutamylamino)Butanoate4-(L-γ-glutamylamino)Butanoic acidg Glutamyl gabag-Glu-gabag-Glutamyl-g aminobutyrateg-Glutamyl-g aminobutyric acidg-Glutamyl-g-aminobutanoateg-Glutamyl-g-aminobutanoic acidg-Glutamyl-g-aminobutyrateg-Glutamyl-g-aminobutyric acidg-Glutamyl-gabag-L-Glu-g-abug-L-Glutamyl-g-aminobutyrateg-L-Glutamyl-g-aminobutyric acidGamma Glutamyl gabaGamma-Glu-gabaGamma-Glutamyl-gabaGamma-Glutamyl-gamma aminobutyrateGamma-Glutamyl-gamma aminobutyric acidGamma-Glutamyl-gamma-aminobutanoateGamma-Glutamyl-gamma-aminobutanoic acidGamma-Glutamyl-gamma-aminobutyrateGamma-Glutamyl-gamma-aminobutyric acidGamma-L-Glu-gamma-abuGamma-L-Glutamyl-gamma-aminobutyrateGamma-L-Glutamyl-gamma-aminobutyric acidGlugabaGlutamylgabaN(5)-(3-Carboxypropyl)-L-glutamineγ Glutamyl gabaγ-Glu-gabaγ-Glutamyl-gabaγ-Glutamyl-γ aminobutyrateγ-Glutamyl-γ aminobutyric acidγ-Glutamyl-γ-aminobutanoateγ-Glutamyl-γ-aminobutanoic acidγ-Glutamyl-γ-aminobutyrateγ-Glutamyl-γ-aminobutyric acidγ-L-Glu-γ-abuγ-L-Glutamyl-γ-aminobutyrateγ-L-Glutamyl-γ-aminobutyric acidC9H16N2O5232.2337232.105921632(2S)-2-amino-4-[(3-carboxypropyl)carbamoyl]butanoic acidglugaba5105-96-4N[C@@H](CCC(=O)NCCCC(O)=O)C(O)=OInChI=1S/C9H16N2O5/c10-6(9(15)16)3-4-7(12)11-5-1-2-8(13)14/h6H,1-5,10H2,(H,11,12)(H,13,14)(H,15,16)/t6-/m0/s1MKYPKZSGLSOGLL-LURJTMIESA-NSolidCytosollogp-3.37logs-1.28solubility1.21e+01 g/llogp-3.9pka_strongest_acidic2.3pka_strongest_basic9.31iupac(2S)-2-amino-4-[(3-carboxypropyl)carbamoyl]butanoic acidaverage_mass232.2337mono_mass232.105921632smilesN[C@@H](CCC(=O)NCCCC(O)=O)C(O)=OformulaC9H16N2O5inchiInChI=1S/C9H16N2O5/c10-6(9(15)16)3-4-7(12)11-5-1-2-8(13)14/h6H,1-5,10H2,(H,11,12)(H,13,14)(H,15,16)/t6-/m0/s1inchikeyMKYPKZSGLSOGLL-LURJTMIESA-Npolar_surface_area129.72refractivity53.55polarizability23.13rotatable_bond_count8acceptor_count6donor_count4physiological_charge-1formal_charge0Arginine and proline metabolismec00330L-glutamate metabolism
There are various ways by which glutamate enters the cytoplasm in E.coli. through a glutamate:sodium symporter, glutamate / aspartate : H+ symporter GltP or a
glutamate / aspartate ABC transporter.
There are various ways by which E. coli synthesizes glutamate from L-glutamine or oxoglutaric acid.
L-glutamine, introduced into the cytoplasm by glutamine ABC transporter, can either interact with glutaminase resulting in ammonia and L-glutamic acid, or react with oxoglutaric acid, and hydrogen ion through an NADPH driven glutamate synthase resulting in L-glutamic acid.
L-glutamic acid is metabolized into L-glutamine by reacting with ammonium through a ATP driven glutamine synthase. L-glutamic acid can also be metabolized into L-aspartic acid by reacting with oxalacetic acid through an aspartate transaminase resulting in n oxoglutaric acid and L-aspartic acid. L-aspartic acid is metabolized into fumaric acid through an
aspartate ammonia-lyase. Fumaric acid can be introduced into the cytoplasm through 3 methods:
dicarboxylate transporter , C4 dicarboxylate / C4 monocarboxylate transporter DauA, and C4 dicarboxylate / orotate:H+ symporter
PW000789Metabolicarginine 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.
PW000791Metabolicputrescine degradation IIPWY0-1221Specdb::CMs2849Specdb::CMs39841Specdb::CMs175409Specdb::NmrOneD95578Specdb::NmrOneD95579Specdb::NmrOneD95580Specdb::NmrOneD95581Specdb::NmrOneD95582Specdb::NmrOneD95583Specdb::NmrOneD95584Specdb::NmrOneD95585Specdb::NmrOneD95586Specdb::NmrOneD95587Specdb::NmrOneD95588Specdb::NmrOneD95589Specdb::NmrOneD95590Specdb::NmrOneD95591Specdb::NmrOneD95592Specdb::NmrOneD95593Specdb::NmrOneD95594Specdb::NmrOneD95595Specdb::NmrOneD95596Specdb::NmrOneD95597Specdb::MsMs27572Specdb::MsMs27573Specdb::MsMs27574Specdb::MsMs34130Specdb::MsMs34131Specdb::MsMs34132Specdb::MsMs2735708Specdb::MsMs2735709Specdb::MsMs2735710Specdb::MsMs2973396Specdb::MsMs2973397Specdb::MsMs2973398HMDB121612372457021865667C1576749260CPD-9000Keseler, 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-D590.21097882Kanehisa, 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-D114.22080510Gamma-glutamyl-gamma-aminobutyraldehyde dehydrogenaseP23883PUUC_ECOLIpuuChttp://ecmdb.ca/proteins/P23883.xmlGlutamate decarboxylase alphaP69908DCEA_ECOLIgadAhttp://ecmdb.ca/proteins/P69908.xmlGlutamate decarboxylase betaP69910DCEB_ECOLIgadBhttp://ecmdb.ca/proteins/P69910.xmlGamma-glutamyl-gamma-aminobutyrate hydrolaseP76038PUUD_ECOLIpuuDhttp://ecmdb.ca/proteins/P76038.xml4-(Glutamylamino) butanoate + Water <> gamma-Aminobutyric acid + L-GlutamateR07419RXN0-3942gamma-Glutamyl-gamma-butyraldehyde + Water + NADP <> 4-(Glutamylamino) butanoate +2 Hydrogen ion + NADPHR07418gamma-Glutamyl-gamma-butyraldehyde + NAD + Water <> 4-(Glutamylamino) butanoate + NADH + Hydrogen ionR07417gamma-Glutamyl-gamma-butyraldehyde + NADP + Water <> 4-(Glutamylamino) butanoate + NADPH + Hydrogen ionR07418NAD(P)<sup>+</sup> + gamma-Glutamyl-gamma-butyraldehyde + Water > 4-(Glutamylamino) butanoate + NAD(P)H + Hydrogen ionRXN0-39224-(Glutamylamino) butanoate + Water > gamma-Aminobutyric acid + L-GlutamateRXN0-3942Gamma-glutamyl-gamma-aminobutyraldehyde + NAD + Water > 4-(Glutamylamino) butanoate + NADHL-Glutamic acid + Hydrogen ion + L-Glutamate > Carbon dioxide + 4-(Glutamylamino) butanoatePW_R0051464-(γ-glutamylamino)butanal + Water + NADP > 4-(Glutamylamino) butanoate +2 Hydrogen ion + NADPH + NADPHPW_R0026874-(Glutamylamino) butanoate + Water > L-Glutamic acid + gamma-Aminobutyric acid + L-GlutamatePW_R002688gamma-Glutamyl-gamma-butyraldehyde + Water + NADP <>4 4-(Glutamylamino) butanoate +2 Hydrogen ion + NADPH