2.0 2012-05-31 13:48:27 -0600 2015-09-13 12:56:10 -0600 ECMDB01257 M2MDB000312 Spermidine Spermidine 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-Triazadecane 1,8-Diamino-4-azaoctane 4-Azaoctamethylenediamine 4-Azaoctane-1,8-diamine <i>N</i>-(3-aminopropyl)butane-1,4-diamine Aminopropylbutandiamine N-(3-Aminopropyl)-1,4-butane-diamine N-(3-Aminopropyl)-1,4-butanediamine N-(3-Aminopropyl)-1,4-diamino-butane N-(3-Aminopropyl)-1,4-diaminobutane N-(3-Aminopropyl)-4-aminobutylamine N-(3-Aminopropyl)butane-1,4-diamine N-(4-Aminobutyl)-1,3-diaminopropane N-(g-Aminopropyl)tetramethylenediamine N-(gamma-Aminopropyl)tetramethylenediamine N-(γ-Aminopropyl)tetramethylenediamine SPD Spermidin Spermidine C7H19N3 145.2459 145.157897623 (4-aminobutyl)(3-aminopropyl)amine spermidine 124-20-9 NCCCCNCCCN InChI=1S/C7H19N3/c8-4-1-2-6-10-7-3-5-9/h10H,1-9H2 ATHGHQPFGPMSJY-UHFFFAOYSA-N Liquid Cytosol Extra-organism Periplasm logp -0.62 ALOGPS logs -0.65 ALOGPS solubility 3.27e+01 g/l ALOGPS melting_point < 25 oC logp -1.1 ChemAxon pka_strongest_basic 10.68 ChemAxon iupac (4-aminobutyl)(3-aminopropyl)amine ChemAxon average_mass 145.2459 ChemAxon mono_mass 145.157897623 ChemAxon smiles NCCCCNCCCN ChemAxon formula C7H19N3 ChemAxon inchi InChI=1S/C7H19N3/c8-4-1-2-6-10-7-3-5-9/h10H,1-9H2 ChemAxon inchikey ATHGHQPFGPMSJY-UHFFFAOYSA-N ChemAxon polar_surface_area 64.07 ChemAxon refractivity 44.97 ChemAxon polarizability 18.8 ChemAxon rotatable_bond_count 7 ChemAxon acceptor_count 3 ChemAxon donor_count 3 ChemAxon physiological_charge 3 ChemAxon formal_charge 0 ChemAxon Glutathione metabolism The 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. PW000833 ec00480 Metabolic Arginine and proline metabolism ec00330 Cysteine and methionine metabolism ec00270 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 ABC transporters ec02010 Metabolic pathways eco01100 S-adenosyl-L-methionine biosynthesis S-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 environment PW000837 Metabolic Spermidine Biosynthesis I Spermidine 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) PW002040 Metabolic Spermidine biosynthesis and metabolism Spermidine 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. PW002085 Metabolic spermidine biosynthesis I BSUBPOLYAMSYN-PWY Specdb::CMs 718 Specdb::CMs 719 Specdb::CMs 720 Specdb::CMs 721 Specdb::CMs 1866 Specdb::CMs 1897 Specdb::CMs 1987 Specdb::CMs 3462 Specdb::CMs 30115 Specdb::CMs 30402 Specdb::CMs 30403 Specdb::CMs 30693 Specdb::CMs 30931 Specdb::CMs 31303 Specdb::CMs 31304 Specdb::CMs 31305 Specdb::CMs 31887 Specdb::CMs 31888 Specdb::CMs 151426 Specdb::NmrOneD 1671 Specdb::NmrOneD 146990 Specdb::NmrOneD 146991 Specdb::NmrOneD 146992 Specdb::NmrOneD 146993 Specdb::NmrOneD 146994 Specdb::NmrOneD 146995 Specdb::NmrOneD 146996 Specdb::NmrOneD 146997 Specdb::NmrOneD 146998 Specdb::NmrOneD 146999 Specdb::NmrOneD 147000 Specdb::NmrOneD 147001 Specdb::NmrOneD 147002 Specdb::NmrOneD 147003 Specdb::NmrOneD 147004 Specdb::NmrOneD 147005 Specdb::NmrOneD 147006 Specdb::NmrOneD 147007 Specdb::NmrOneD 147008 Specdb::NmrOneD 147009 Specdb::MsMs 1490 Specdb::MsMs 1491 Specdb::MsMs 1492 Specdb::MsMs 5144 Specdb::MsMs 5145 Specdb::MsMs 5146 Specdb::MsMs 5147 Specdb::MsMs 5148 Specdb::MsMs 5149 Specdb::MsMs 5150 Specdb::MsMs 5151 Specdb::MsMs 5152 Specdb::MsMs 5153 Specdb::MsMs 5154 Specdb::MsMs 5155 Specdb::MsMs 5156 Specdb::MsMs 20549 Specdb::MsMs 20550 Specdb::MsMs 20551 Specdb::MsMs 22100 Specdb::MsMs 22101 Specdb::MsMs 22102 Specdb::MsMs 445244 Specdb::MsMs 445245 Specdb::MsMs 445246 Specdb::NmrTwoD 1062 Specdb::NmrTwoD 1612 HMDB01257 1102 1071 C00315 1643 SPERMIDINE SPD Spermidine 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 Vijayendran, 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. 18402659 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). "Global metabolic profiling of Escherichia coli cultures: an evaluation of methods for quenching and extraction of intracellular metabolites." Anal Chem 80:2939-2948. 18331064 Hamana, K. (1996). "Distribution of diaminopropane and acetylspermidine in Enterobacteriaceae." Can J Microbiol 42:107-114. 8742354 Sreekumar 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. 19212411 Venza 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. 11419735 Uehara 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. 7350997 Proctor 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. 1176793 El 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. 6625645 Mirzoian 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. 516181 Chaisiri 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. 6156039 Martinet 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. 2241917 Bergeron, 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?1358461274 Spermidine synthase P09158 SPEE_ECOLI speE http://ecmdb.ca/proteins/P09158.xml Spermidine N(1)-acetyltransferase P0A951 ATDA_ECOLI speG http://ecmdb.ca/proteins/P0A951.xml Bifunctional glutathionylspermidine synthetase/amidase P0AES0 GSP_ECOLI gsp http://ecmdb.ca/proteins/P0AES0.xml Spermidine/putrescine import ATP-binding protein PotA P69874 POTA_ECOLI potA http://ecmdb.ca/proteins/P69874.xml Putative ABC transporter periplasmic-binding protein ydcS P76108 YDCS_ECOLI ydcS http://ecmdb.ca/proteins/P76108.xml Uncharacterized ABC transporter ATP-binding protein ydcT P77795 YDCT_ECOLI ydcT http://ecmdb.ca/proteins/P77795.xml Inner membrane ABC transporter permease protein ydcU P77156 YDCU_ECOLI ydcU http://ecmdb.ca/proteins/P77156.xml Inner membrane ABC transporter permease protein ydcV P0AFR9 YDCV_ECOLI ydcV http://ecmdb.ca/proteins/P0AFR9.xml Spermidine/putrescine transport system permease protein potB P0AFK4 POTB_ECOLI potB http://ecmdb.ca/proteins/P0AFK4.xml Spermidine/putrescine transport system permease protein potC P0AFK6 POTC_ECOLI potC http://ecmdb.ca/proteins/P0AFK6.xml Spermidine/putrescine-binding periplasmic protein P0AFK9 POTD_ECOLI potD http://ecmdb.ca/proteins/P0AFK9.xml Spermidine/putrescine import ATP-binding protein PotA P69874 POTA_ECOLI potA http://ecmdb.ca/proteins/P69874.xml Putative ABC transporter periplasmic-binding protein ydcS P76108 YDCS_ECOLI ydcS http://ecmdb.ca/proteins/P76108.xml Uncharacterized ABC transporter ATP-binding protein ydcT P77795 YDCT_ECOLI ydcT http://ecmdb.ca/proteins/P77795.xml Inner membrane ABC transporter permease protein ydcU P77156 YDCU_ECOLI ydcU http://ecmdb.ca/proteins/P77156.xml Inner membrane ABC transporter permease protein ydcV P0AFR9 YDCV_ECOLI ydcV http://ecmdb.ca/proteins/P0AFR9.xml Spermidine/putrescine transport system permease protein potB P0AFK4 POTB_ECOLI potB http://ecmdb.ca/proteins/P0AFK4.xml Spermidine/putrescine transport system permease protein potC P0AFK6 POTC_ECOLI potC http://ecmdb.ca/proteins/P0AFK6.xml Spermidine export protein mdtI P69210 MDTI_ECOLI mdtI http://ecmdb.ca/proteins/P69210.xml Spermidine export protein mdtJ P69212 MDTJ_ECOLI mdtJ http://ecmdb.ca/proteins/P69212.xml Outer membrane protein N P77747 OMPN_ECOLI ompN http://ecmdb.ca/proteins/P77747.xml Outer membrane pore protein E P02932 PHOE_ECOLI phoE http://ecmdb.ca/proteins/P02932.xml Outer membrane protein F P02931 OMPF_ECOLI ompF http://ecmdb.ca/proteins/P02931.xml Outer membrane protein C P06996 OMPC_ECOLI ompC http://ecmdb.ca/proteins/P06996.xml Spermidine/putrescine-binding periplasmic protein P0AFK9 POTD_ECOLI potD http://ecmdb.ca/proteins/P0AFK9.xml Adenosine triphosphate + Water + Spermidine > ADP + Hydrogen ion + Phosphate + Spermidine ABC-24-RXN Adenosine triphosphate + Water + Spermidine > ADP + Hydrogen ion + Phosphate + Spermidine ABC-24-RXN S-Adenosylmethioninamine + Putrescine + Ethylenediamine <> 5'-Methylthioadenosine + Hydrogen ion + Spermidine R01920 SPERMIDINESYN-RXN Acetyl-CoA + Spermidine > N1-Acetylspermidine + Coenzyme A + Hydrogen ion SPERMACTRAN-RXN Acetyl-CoA + Spermidine > Coenzyme A + Hydrogen ion + N8-Acetylspermidine Adenosine triphosphate + Glutathione + Spermidine <> ADP + Glutathionylspermidine + Hydrogen ion + Phosphate R01917 GSPSYN-RXN Glutathionylspermidine + Water <> Glutathione + Spermidine R01918 GSPAMID-RXN Adenosine triphosphate + Glutathione + Spermidine <> ADP + Phosphate + Glutathionylspermidine R01917 S-Adenosylmethioninamine + Putrescine <> 5'-Methylthioadenosine + Spermidine R01920 SPERMIDINESYN-RXN S-Adenosylmethioninamine + Spermidine <> 5'-Methylthioadenosine + Spermine R02869 Adenosine triphosphate + Spermidine + Water > ADP + Phosphate + Spermidine + Hydrogen ion ABC-24-RXN Adenosine triphosphate + Spermidine + Water > ADP + Phosphate + Spermidine + Hydrogen ion ABC-24-RXN Glutathionylspermidine + Water > Glutathione + Spermidine GSPAMID-RXN Spermidine + Glutathione + Adenosine triphosphate > Hydrogen ion + Glutathionylspermidine + ADP + Phosphate GSPSYN-RXN Acetyl-CoA + Spermidine <> N1-Acetylspermidine + Hydrogen ion + Coenzyme A SPERMACTRAN-RXN Putrescine + S-Adenosylmethioninamine > Hydrogen ion + Spermidine + 5'-Methylthioadenosine SPERMIDINESYN-RXN Glutathione + Spermidine + Adenosine triphosphate > Glutathionylspermidine + ADP + Inorganic phosphate S-Adenosylmethioninamine + Putrescine > 5'-Methylthioadenosine + Spermidine Putrescine + S-Adenosylmethioninamine > Spermidine + Hydrogen ion + 5'-S-methyl-5'-thioadenosine PW_R005166 Decarboxy-SAM + Putrescine > 5'-Methylthioadenosine + Spermidine + Hydrogen ion PW_R005961 S-Adenosylmethioninamine + Putrescine + Ethylenediamine <>5 5'-Methylthioadenosine + Hydrogen ion + Spermidine S-Adenosylmethioninamine + Putrescine + Ethylenediamine <>5 5'-Methylthioadenosine + Hydrogen ion + Spermidine 199 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)3 Shake flask 2720.0 uM 0.0 37 oC K12 HB101 Mid Log Phase 10880000 0 Hamana, K. (1996). "Distribution of diaminopropane and acetylspermidine in Enterobacteriaceae." Can J Microbiol 42:107-114. 8742354 199 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)3 Shake flask 130.0 uM 0.0 37 oC K12 HB101 Stationary Phase 520000 0 Hamana, K. (1996). "Distribution of diaminopropane and acetylspermidine in Enterobacteriaceae." Can J Microbiol 42:107-114. 8742354