2.02012-05-31 13:52:33 -06002015-09-13 12:56:11 -0600ECMDB01432M2MDB000385AgmatineAgmatine (also known as (4-aminobutyl)guanidine) is the decarboxylation product of the amino acid arginine and is an intermediate in polyamine biosynthesis. (Wikipedia) In E. coli arginine metabolism, agmatine is produced from arginine in a reaction catalyzed by arginine decarboxylase (4.1.1.19). Another enzyme, agmatinase (EC 3.5.3.11), can then convert agmatine to putrescine, which is a polyamine that can be further converted to other products such as spermidine. (KEGG)(4-aminobutyl)-Guanidine(4-Aminobutyl)guanidine1-(4-Aminobutyl)guanidine1-Amino-4-guanidinobutane1-Amino-4-guanidobutane4-Guanidino-1-butanamineAgmatineArgmatineN-(4-Aminobutyl)guanidineN-(Aminoiminomethyl)-1,4-ButanediamineN-4-AminobutylguanidineC5H14N4130.1915130.121846468N-(4-aminobutyl)guanidineagmatine306-60-5NCCCCNC(N)=NInChI=1S/C5H14N4/c6-3-1-2-4-9-5(7)8/h1-4,6H2,(H4,7,8,9)QYPPJABKJHAVHS-UHFFFAOYSA-NSolidCytosolExtra-organismPeriplasmlogp-1.01logs-1.56solubility3.61e+00 g/llogp-1.2pka_strongest_basic12.61iupacN-(4-aminobutyl)guanidineaverage_mass130.1915mono_mass130.121846468smilesNCCCCNC(N)=NformulaC5H14N4inchiInChI=1S/C5H14N4/c6-3-1-2-4-9-5(7)8/h1-4,6H2,(H4,7,8,9)inchikeyQYPPJABKJHAVHS-UHFFFAOYSA-Npolar_surface_area87.92refractivity48.09polarizability15.01rotatable_bond_count4acceptor_count4donor_count4physiological_charge2formal_charge0Arginine and proline metabolismec00330Metabolic 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 cyclePW000790Metabolicarginine degradation III (arginine decarboxylase/agmatinase pathway)PWY0-823putrescine biosynthesis IPWY-40arginine dependent acid resistancePWY0-1299Specdb::CMs751Specdb::CMs752Specdb::CMs1399Specdb::CMs5906Specdb::CMs31334Specdb::CMs31686Specdb::CMs148603Specdb::NmrOneD1706Specdb::NmrOneD9322Specdb::NmrOneD9323Specdb::NmrOneD9324Specdb::NmrOneD9325Specdb::NmrOneD9326Specdb::NmrOneD9327Specdb::NmrOneD9328Specdb::NmrOneD9329Specdb::NmrOneD9330Specdb::NmrOneD9331Specdb::NmrOneD9332Specdb::NmrOneD9333Specdb::NmrOneD9334Specdb::NmrOneD9335Specdb::NmrOneD9336Specdb::NmrOneD9337Specdb::NmrOneD9338Specdb::NmrOneD9339Specdb::NmrOneD9340Specdb::NmrOneD9341Specdb::NmrOneD166611Specdb::MsMs1577Specdb::MsMs1578Specdb::MsMs1579Specdb::MsMs5313Specdb::MsMs5314Specdb::MsMs5315Specdb::MsMs5316Specdb::MsMs5317Specdb::MsMs5320Specdb::MsMs5321Specdb::MsMs21335Specdb::MsMs21336Specdb::MsMs21337Specdb::MsMs22886Specdb::MsMs22887Specdb::MsMs22888Specdb::MsMs441451Specdb::MsMs445666Specdb::MsMs445667Specdb::MsMs445668Specdb::MsMs445669Specdb::MsMs445670Specdb::MsMs447959Specdb::MsMs448128Specdb::MsMs451914Specdb::NmrTwoD1072Specdb::NmrTwoD1647HMDB01432199194C0017917431AGMATHINEAG2AgmatineKeseler, 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-D114.22080510van 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 370:17-25.17765195Winder, C. L., Dunn, W. B., Schuler, S., Broadhurst, D., Jarvis, R., Stephens, G. M., Goodacre, R. (2008). "Global metabolic profiling of Escherichia coli cultures: an evaluation of methods for quenching and extraction of intracellular metabolites." Anal Chem 80:2939-2948.18331064Hamana, K. (1996). "Distribution of diaminopropane and acetylspermidine in Enterobacteriaceae." Can J Microbiol 42:107-114.8742354Thiele I, Swainston N, Fleming RM, Hoppe A, Sahoo S, Aurich MK, Haraldsdottir H, Mo ML, Rolfsson O, Stobbe MD, Thorleifsson SG, Agren R, Bolling C, Bordel S, Chavali AK, Dobson P, Dunn WB, Endler L, Hala D, Hucka M, Hull D, Jameson D, Jamshidi N, Jonsson JJ, Juty N, Keating S, Nookaew I, Le Novere N, Malys N, Mazein A, Papin JA, Price ND, Selkov E Sr, Sigurdsson MI, Simeonidis E, Sonnenschein N, Smallbone K, Sorokin A, van Beek JH, Weichart D, Goryanin I, Nielsen J, Westerhoff HV, Kell DB, Mendes P, Palsson BO: A community-driven global reconstruction of human metabolism. Nat Biotechnol. 2013 Mar 3. doi: 10.1038/nbt.2488.23455439Halaris A, Piletz JE: Relevance of imidazoline receptors and agmatine to psychiatry: a decade of progress. Ann N Y Acad Sci. 2003 Dec;1009:1-20.15028565Feng Y, Halaris AE, Piletz JE: Determination of agmatine in brain and plasma using high-performance liquid chromatography with fluorescence detection. J Chromatogr B Biomed Sci Appl. 1997 Apr 11;691(2):277-86.9174263Atlas D: Molecular and physiological properties of clonidine-displacing substance. Ann N Y Acad Sci. 1995 Jul 12;763:314-24.7677341Zhao S, Wang B, Yuan H, Xiao D: Determination of agmatine in biological samples by capillary electrophoresis with optical fiber light-emitting-diode-induced fluorescence detection. J Chromatogr A. 2006 Aug 4;1123(1):138-41. Epub 2006 Jul 3.16820162http://hmdb.ca/system/metabolites/msds/000/001/294/original/HMDB01432.pdf?1358462635Biosynthetic arginine decarboxylaseP21170SPEA_ECOLIspeAhttp://ecmdb.ca/proteins/P21170.xmlBiodegradative arginine decarboxylaseP28629ADIA_ECOLIadiAhttp://ecmdb.ca/proteins/P28629.xmlAgmatinaseP60651SPEB_ECOLIspeBhttp://ecmdb.ca/proteins/P60651.xmlOuter membrane protein NP77747OMPN_ECOLIompNhttp://ecmdb.ca/proteins/P77747.xmlOuter membrane pore protein EP02932PHOE_ECOLIphoEhttp://ecmdb.ca/proteins/P02932.xmlArginine/agmatine antiporterP60061ADIC_ECOLIadiChttp://ecmdb.ca/proteins/P60061.xmlOuter membrane protein FP02931OMPF_ECOLIompFhttp://ecmdb.ca/proteins/P02931.xmlOuter membrane protein CP06996OMPC_ECOLIompChttp://ecmdb.ca/proteins/P06996.xmlAgmatine + Water <> Putrescine + Urea + EthylenediamineR01157AGMATIN-RXNL-Arginine + Hydrogen ion <> Agmatine + Carbon dioxideR00566ARGDECARBOX-RXNL-Arginine + Hydrogen ion > Agmatine + Carbon dioxideL-Arginine <> Agmatine + Carbon dioxideR00566Agmatine + Water <> Putrescine + UreaR01157Water + Agmatine > Urea + PutrescineAGMATIN-RXNL-Arginine > Agmatine + Carbon dioxideL-Arginine + Hydrogen ion + Carbon dioxide > AgmatinePW_R002683L-Arginine + Hydrogen ion <> Agmatine + Carbon dioxideL-Arginine + Hydrogen ion <> Agmatine + Carbon dioxide199 Medium with Earle’s salts –which contains 21 amino acids, 17 vitamins, 10 components of nucleic acids, sodium acetate, glucose, NaC1, KCl, CaC12, MgS04, Na2HP04, and Fe(N03)3Shake flask10.0uM0.037 oCK12 HB101Mid Log Phase400000Hamana, K. (1996). "Distribution of diaminopropane and acetylspermidine in Enterobacteriaceae." Can J Microbiol 42:107-114.8742354199 Medium with Earle’s salts –which contains 21 amino acids, 17 vitamins, 10 components of nucleic acids, sodium acetate, glucose, NaC1, KCl, CaC12, MgS04, Na2HP04, and Fe(N03)3Shake flask110.0uM0.037 oCK12 HB101Stationary Phase4400000Hamana, K. (1996). "Distribution of diaminopropane and acetylspermidine in Enterobacteriaceae." Can J Microbiol 42:107-114.8742354