2.02012-05-31 13:48:27 -06002015-09-13 12:56:10 -0600ECMDB01257M2MDB000312SpermidineSpermidine is a polyamine formed from putrescine. It is found in almost all tissues in association with nucleic acids. It is found as a cation at all pH values, and is thought to help stabilize some membranes and nucleic acid structures. It is a precursor of spermine.1,5,10-Triazadecane1,8-Diamino-4-azaoctane4-Azaoctamethylenediamine4-Azaoctane-1,8-diamine<i>N</i>-(3-aminopropyl)butane-1,4-diamineAminopropylbutandiamineN-(3-Aminopropyl)-1,4-butane-diamineN-(3-Aminopropyl)-1,4-butanediamineN-(3-Aminopropyl)-1,4-diamino-butaneN-(3-Aminopropyl)-1,4-diaminobutaneN-(3-Aminopropyl)-4-aminobutylamineN-(3-Aminopropyl)butane-1,4-diamineN-(4-Aminobutyl)-1,3-diaminopropaneN-(g-Aminopropyl)tetramethylenediamineN-(gamma-Aminopropyl)tetramethylenediamineN-(γ-Aminopropyl)tetramethylenediamineSPDSpermidinSpermidineC7H19N3145.2459145.157897623(4-aminobutyl)(3-aminopropyl)aminespermidine124-20-9NCCCCNCCCNInChI=1S/C7H19N3/c8-4-1-2-6-10-7-3-5-9/h10H,1-9H2ATHGHQPFGPMSJY-UHFFFAOYSA-NLiquidCytosolExtra-organismPeriplasmlogp-0.62logs-0.65solubility3.27e+01 g/lmelting_point< 25 oClogp-1.1pka_strongest_basic10.68iupac(4-aminobutyl)(3-aminopropyl)amineaverage_mass145.2459mono_mass145.157897623smilesNCCCCNCCCNformulaC7H19N3inchiInChI=1S/C7H19N3/c8-4-1-2-6-10-7-3-5-9/h10H,1-9H2inchikeyATHGHQPFGPMSJY-UHFFFAOYSA-Npolar_surface_area64.07refractivity44.97polarizability18.8rotatable_bond_count7acceptor_count3donor_count3physiological_charge3formal_charge0Glutathione metabolismThe biosynthesis of glutathione starts with the introduction of L-glutamic acid through either a glutamate:sodium symporter, glutamate / aspartate : H+ symporter GltP or a
glutamate / aspartate ABC transporter. Once in the cytoplasm, L-glutamice acid reacts with L-cysteine through an ATP glutamate-cysteine ligase resulting in gamma-glutamylcysteine. This compound reacts which Glycine through an ATP driven glutathione synthetase thus catabolizing Glutathione.
This compound is metabolized through a spontaneous reaction with an oxidized glutaredoxin resulting in a reduced glutaredoxin and an oxidized glutathione. This compound is reduced by a NADPH glutathione reductase resulting in a glutathione.
PW000833ec00480MetabolicArginine and proline metabolismec00330Cysteine and methionine metabolismec00270beta-Alanine metabolismThe 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.PW000896ec00410MetabolicABC transportersec02010Metabolic pathwayseco01100S-adenosyl-L-methionine biosynthesisS-adenosyl-L-methionine biosynthesis(SAM) is synthesized in the cytosol of the cell from L-methionine and ATP. This reaction is catalyzed by methionine adenosyltransferase. L methione is taken up from the environment through a complex reaction coupled transport and then proceeds too synthesize the s adenosylmethionine through a adenosylmethionine synthase. The S-adenosylmethionine then interacts with a hydrogen ion through a adenosylmethionine decarboxylase resulting in a carbon dioxide and a S-adenosyl 3-methioninamine.This compound interacts with a putrescine through a spermidine synthase resulting in a spermidine, a hydrogen ion and a S-methyl-5'-thioadenosine. The latter compound is degraded by interacting with a water molecule through a 5' methylthioadenosine nucleosidase resulting in a adenine and a S-methylthioribose which is then release into the environmentPW000837MetabolicSpermidine Biosynthesis ISpermidine is formed by the addition of a propylamine moiety to putrescine, catalyzed by an aminopropyltransferase termed spermidine synthase, the the product of gene speE. The source of the propylamine group is decarboxylated S-adenosyl-L-methionine (S-adenosyl-L-methioninamine) which is produced by the action of the pyruvoyl-containing enzyme adenosylmethionine decarboxylase. The other product of the aminopropyltransferase reaction is S-methyl-5'-thioadenosine (MTA), which can be recycled back to L-methionine in many organisms, but not in E. coli.
Inhibition of E. coli adenosylmethionine decarboxylase by spermidine appears to be the most significant regulator of polyamine biosynthesis, probably limiting it when the intracellular spermidine concentration becomes excessive. In E. coli most intracellular spermidine is bound to nucleic acids and phospholipids. (EcoCyc)PW002040MetabolicSpermidine biosynthesis and metabolismSpermidine metabolism starts with S-adenosyl-L-methionine reacting with a hydrogen ion through a adenosylmethionine decarboxylase resulting in the release of a carbon dioxide and a S-adenosyl 3-(methylthio)propylamine. The later compound in turn reacts with putrescine resulting in the release of a hydrogen ion, a spermidine and a S-methyl-5'-thioadenosine. S-methyl-5'-thioadenosine in turn reacts with a water molecule through a 5-methylthioadenosine nucleosidase resulting in the release of a adenine and a S-methyl-5-thio-D-ribose which in in turn is released into the environment. PW002085Metabolicspermidine biosynthesis IBSUBPOLYAMSYN-PWYSpecdb::CMs718Specdb::CMs719Specdb::CMs720Specdb::CMs721Specdb::CMs1866Specdb::CMs1897Specdb::CMs1987Specdb::CMs3462Specdb::CMs30115Specdb::CMs30402Specdb::CMs30403Specdb::CMs30693Specdb::CMs30931Specdb::CMs31303Specdb::CMs31304Specdb::CMs31305Specdb::CMs31887Specdb::CMs31888Specdb::CMs151426Specdb::NmrOneD1671Specdb::NmrOneD146990Specdb::NmrOneD146991Specdb::NmrOneD146992Specdb::NmrOneD146993Specdb::NmrOneD146994Specdb::NmrOneD146995Specdb::NmrOneD146996Specdb::NmrOneD146997Specdb::NmrOneD146998Specdb::NmrOneD146999Specdb::NmrOneD147000Specdb::NmrOneD147001Specdb::NmrOneD147002Specdb::NmrOneD147003Specdb::NmrOneD147004Specdb::NmrOneD147005Specdb::NmrOneD147006Specdb::NmrOneD147007Specdb::NmrOneD147008Specdb::NmrOneD147009Specdb::MsMs1490Specdb::MsMs1491Specdb::MsMs1492Specdb::MsMs5144Specdb::MsMs5145Specdb::MsMs5146Specdb::MsMs5147Specdb::MsMs5148Specdb::MsMs5149Specdb::MsMs5150Specdb::MsMs5151Specdb::MsMs5152Specdb::MsMs5153Specdb::MsMs5154Specdb::MsMs5155Specdb::MsMs5156Specdb::MsMs20549Specdb::MsMs20550Specdb::MsMs20551Specdb::MsMs22100Specdb::MsMs22101Specdb::MsMs22102Specdb::MsMs445244Specdb::MsMs445245Specdb::MsMs445246Specdb::NmrTwoD1062Specdb::NmrTwoD1612HMDB0125711021071C003151643SPERMIDINESPDSpermidineKeseler, 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-D114.22080510Vijayendran, C., Barsch, A., Friehs, K., Niehaus, K., Becker, A., Flaschel, E. (2008). "Perceiving molecular evolution processes in Escherichia coli by comprehensive metabolite and gene expression profiling." Genome Biol 9:R72.18402659van 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 42:107-114.8742354Sreekumar A, Poisson LM, Rajendiran TM, Khan AP, Cao Q, Yu J, Laxman B, Mehra R, Lonigro RJ, Li Y, Nyati MK, Ahsan A, Kalyana-Sundaram S, Han B, Cao X, Byun J, Omenn GS, Ghosh D, Pennathur S, Alexander DC, Berger A, Shuster JR, Wei JT, Varambally S, Beecher C, Chinnaiyan AM: Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature. 2009 Feb 12;457(7231):910-4.19212411Venza M, Visalli M, Cicciu D, Teti D: Determination of polyamines in human saliva by high-performance liquid chromatography with fluorescence detection. J Chromatogr B Biomed Sci Appl. 2001 Jun 5;757(1):111-7.11419735Uehara N, Shirakawa S, Uchino H, Saeki Y: Elevated contents of spermidine and spermine in the erythrocytes of cancer patients. Cancer. 1980 Jan 1;45(1):108-11.7350997Proctor MS, Fletcher HV Jr, Shukla JB, Rennert OM: Elevated spermidine and spermine levels in the blood of psoriasis patients. J Invest Dermatol. 1975 Oct;65(4):409-11.1176793El Baze P, Milano G, Verrando P, Renee N, Ortonne JP: Polyamine levels in normal human skin. A comparative study of pure epidermis, pure dermis, and suction blister fluid. Arch Dermatol Res. 1983;275(4):218-21.6625645Mirzoian PA, Promyslov MSh: [Contents of putrescine, spermidine and spermine in tissue of the human brain glial tumors] Ukr Biokhim Zh. 1979 Sep-Oct;51(5):474-6.516181Chaisiri P, Harper ME, Blamey RW, Peeling WB, Griffiths K: Plasma spermidine concentrations in patients with tumours of the breast or prostate or testis. Clin Chim Acta. 1980 Jul 1;104(3):367-75.6156039Martinet N, Beninati S, Nigra TP, Folk JE: N1N8-bis(gamma-glutamyl)spermidine cross-linking in epidermal-cell envelopes. Comparison of cross-link levels in normal and psoriatic cell envelopes. Biochem J. 1990 Oct 15;271(2):305-8.2241917Bergeron, Raymond J., Jr. Preparation and formulation spermidine analogues for pharmaceutical use as tumor growth inhibitors. U.S. (2001), 31 pp.http://hmdb.ca/system/metabolites/msds/000/001/125/original/HMDB01257.pdf?1358461274Spermidine synthaseP09158SPEE_ECOLIspeEhttp://ecmdb.ca/proteins/P09158.xmlSpermidine N(1)-acetyltransferaseP0A951ATDA_ECOLIspeGhttp://ecmdb.ca/proteins/P0A951.xmlBifunctional glutathionylspermidine synthetase/amidaseP0AES0GSP_ECOLIgsphttp://ecmdb.ca/proteins/P0AES0.xmlSpermidine/putrescine import ATP-binding protein PotAP69874POTA_ECOLIpotAhttp://ecmdb.ca/proteins/P69874.xmlPutative ABC transporter periplasmic-binding protein ydcSP76108YDCS_ECOLIydcShttp://ecmdb.ca/proteins/P76108.xmlUncharacterized ABC transporter ATP-binding protein ydcTP77795YDCT_ECOLIydcThttp://ecmdb.ca/proteins/P77795.xmlInner membrane ABC transporter permease protein ydcUP77156YDCU_ECOLIydcUhttp://ecmdb.ca/proteins/P77156.xmlInner membrane ABC transporter permease protein ydcVP0AFR9YDCV_ECOLIydcVhttp://ecmdb.ca/proteins/P0AFR9.xmlSpermidine/putrescine transport system permease protein potBP0AFK4POTB_ECOLIpotBhttp://ecmdb.ca/proteins/P0AFK4.xmlSpermidine/putrescine transport system permease protein potCP0AFK6POTC_ECOLIpotChttp://ecmdb.ca/proteins/P0AFK6.xmlSpermidine/putrescine-binding periplasmic proteinP0AFK9POTD_ECOLIpotDhttp://ecmdb.ca/proteins/P0AFK9.xmlSpermidine/putrescine import ATP-binding protein PotAP69874POTA_ECOLIpotAhttp://ecmdb.ca/proteins/P69874.xmlPutative ABC transporter periplasmic-binding protein ydcSP76108YDCS_ECOLIydcShttp://ecmdb.ca/proteins/P76108.xmlUncharacterized ABC transporter ATP-binding protein ydcTP77795YDCT_ECOLIydcThttp://ecmdb.ca/proteins/P77795.xmlInner membrane ABC transporter permease protein ydcUP77156YDCU_ECOLIydcUhttp://ecmdb.ca/proteins/P77156.xmlInner membrane ABC transporter permease protein ydcVP0AFR9YDCV_ECOLIydcVhttp://ecmdb.ca/proteins/P0AFR9.xmlSpermidine/putrescine transport system permease protein potBP0AFK4POTB_ECOLIpotBhttp://ecmdb.ca/proteins/P0AFK4.xmlSpermidine/putrescine transport system permease protein potCP0AFK6POTC_ECOLIpotChttp://ecmdb.ca/proteins/P0AFK6.xmlSpermidine export protein mdtIP69210MDTI_ECOLImdtIhttp://ecmdb.ca/proteins/P69210.xmlSpermidine export protein mdtJP69212MDTJ_ECOLImdtJhttp://ecmdb.ca/proteins/P69212.xmlOuter membrane protein NP77747OMPN_ECOLIompNhttp://ecmdb.ca/proteins/P77747.xmlOuter membrane pore protein EP02932PHOE_ECOLIphoEhttp://ecmdb.ca/proteins/P02932.xmlOuter membrane protein FP02931OMPF_ECOLIompFhttp://ecmdb.ca/proteins/P02931.xmlOuter membrane protein CP06996OMPC_ECOLIompChttp://ecmdb.ca/proteins/P06996.xmlSpermidine/putrescine-binding periplasmic proteinP0AFK9POTD_ECOLIpotDhttp://ecmdb.ca/proteins/P0AFK9.xmlAdenosine triphosphate + Water + Spermidine > ADP + Hydrogen ion + Phosphate + SpermidineABC-24-RXNAdenosine triphosphate + Water + Spermidine > ADP + Hydrogen ion + Phosphate + SpermidineABC-24-RXNS-Adenosylmethioninamine + Putrescine + Ethylenediamine <> 5'-Methylthioadenosine + Hydrogen ion + SpermidineR01920SPERMIDINESYN-RXNAcetyl-CoA + Spermidine > N1-Acetylspermidine + Coenzyme A + Hydrogen ionSPERMACTRAN-RXNAcetyl-CoA + Spermidine > Coenzyme A + Hydrogen ion + N8-AcetylspermidineAdenosine triphosphate + Glutathione + Spermidine <> ADP + Glutathionylspermidine + Hydrogen ion + PhosphateR01917GSPSYN-RXNGlutathionylspermidine + Water <> Glutathione + SpermidineR01918GSPAMID-RXNAdenosine triphosphate + Glutathione + Spermidine <> ADP + Phosphate + GlutathionylspermidineR01917S-Adenosylmethioninamine + Putrescine <> 5'-Methylthioadenosine + SpermidineR01920SPERMIDINESYN-RXNS-Adenosylmethioninamine + Spermidine <> 5'-Methylthioadenosine + SpermineR02869Adenosine triphosphate + Spermidine + Water > ADP + Phosphate + Spermidine + Hydrogen ionABC-24-RXNAdenosine triphosphate + Spermidine + Water > ADP + Phosphate + Spermidine + Hydrogen ionABC-24-RXNGlutathionylspermidine + Water > Glutathione + SpermidineGSPAMID-RXNSpermidine + Glutathione + Adenosine triphosphate > Hydrogen ion + Glutathionylspermidine + ADP + PhosphateGSPSYN-RXNAcetyl-CoA + Spermidine <> N1-Acetylspermidine + Hydrogen ion + Coenzyme ASPERMACTRAN-RXNPutrescine + S-Adenosylmethioninamine > Hydrogen ion + Spermidine + 5'-MethylthioadenosineSPERMIDINESYN-RXNGlutathione + Spermidine + Adenosine triphosphate > Glutathionylspermidine + ADP + Inorganic phosphateS-Adenosylmethioninamine + Putrescine > 5'-Methylthioadenosine + SpermidinePutrescine + S-Adenosylmethioninamine > Spermidine + Hydrogen ion + 5'-S-methyl-5'-thioadenosinePW_R005166Decarboxy-SAM + Putrescine > 5'-Methylthioadenosine + Spermidine + Hydrogen ionPW_R005961S-Adenosylmethioninamine + Putrescine + Ethylenediamine <>5 5'-Methylthioadenosine + Hydrogen ion + SpermidineS-Adenosylmethioninamine + Putrescine + Ethylenediamine <>5 5'-Methylthioadenosine + Hydrogen ion + Spermidine199 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 flask2720.0uM0.037 oCK12 HB101Mid Log Phase108800000Hamana, 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 flask130.0uM0.037 oCK12 HB101Stationary Phase5200000Hamana, K. (1996). "Distribution of diaminopropane and acetylspermidine in Enterobacteriaceae." Can J Microbiol 42:107-114.8742354