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Identification
Name Spermine
Accession Number DB00127 (DB02564, EXPT02947, NUTR00055)
Type small molecule
Groups approved, nutraceutical
Description

A biogenic polyamine formed from spermidine. It is found in a wide variety of organisms and tissues and is an essential growth factor in some bacteria. It is found as a polycation at all pH values. Spermine is associated with nucleic acids, particularly in viruses, and is thought to stabilize the helical structure. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
1, 4-Bis(aminopropyl)butanediamine
4,9-Diaza-1,12-dodecanediamine
4,9-Diazadodecane-1,12-diamine
Spermin
Spermine dihydrate
Salts Not Available
Brand names
Name Company
Gerontine
Musculamine
Neuridine
Brand mixtures Not Available
Categories
  • Dietary supplement
  • Micronutrient
CAS number 71-44-3
Weight Average: 202.3402
Monoisotopic: 202.215746852
Chemical Formula C10H26N4
InChI Key InChIKey=PFNFFQXMRSDOHW-UHFFFAOYSA-N
InChI
InChI=1S/C10H26N4/c11-5-3-9-13-7-1-2-8-14-10-4-6-12/h13-14H,1-12H2
Plain Text
IUPAC Name
(3-aminopropyl)({4-[(3-aminopropyl)amino]butyl})amine
SMILES
NCCCNCCCCNCCCN
Plain Text
Mass Spec show (10.5 KB)
Taxonomy
Kingdom Organic
Classes
  • Aliphatic and Aryl Amines
Substructures
  • Aliphatic and Aryl Amines
Pharmacology
Indication For nutritional supplementation, also for treating dietary shortage or imbalance
Pharmacodynamics Spermine is a polyamine. It is an organic molecule that is involved in cellular metabolism.
Mechanism of action Spermine is derived from spermidine by spermine synthase. Spermine is a polyamine, a small organic cations that is absolutely required for eukaryotic cell growth. Spermine, is normally found in millimolar concentrations in the nucleus. Spermine functions directly as a free radical scavenger, and forms a variety of adducts that prevent oxidative damage to DNA. Oxidative damage to DNA by reactive oxygen species is a continual problem that cells must guard against to survive. Hence, spermine is a major natural intracellular compound capable of protecting DNA from free radical attack. Spermine is also implicated in the regulation of gene expression, the stabilization of chromatin, and the prevention of endonuclease-mediated DNA fragmentation.
Absorption Not Available
Volume of distribution Not Available
Protein binding Not Available
Metabolism Not Available
Route of elimination Not Available
Half life Not Available
Clearance Not Available
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers Not Available
Packagers Not Available
Dosage forms Not Available
Prices Not Available
Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
melting point 29 °C PhysProp
boiling point 150-150 °C Not Available
water solubility > 100 mg/mL Not Available
logP -0.7 Not Available
Predicted Properties
Property Value Source
water solubility 2.19e+00 g/l ALOGPS
logP -0.66 ALOGPS
logP -1.5 ChemAxon
logS -2 ALOGPS
pKa (strongest basic) 11.1 ChemAxon
physiological charge 4 ChemAxon
hydrogen acceptor count 4 ChemAxon
hydrogen donor count 4 ChemAxon
polar surface area 76.1 ChemAxon
rotatable bond count 11 ChemAxon
refractivity 62.56 ChemAxon
polarizability 26.69 ChemAxon
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Compound C00750 Link_out
PubChem Compound 1103 Link_out
PubChem Substance 46507215 Link_out
ChemSpider 1072 Link_out
ChEBI 15746 Link_out
ChEMBL 15746 Link_out
PharmGKB PA164781199 Link_out
IUPHAR 710 Link_out
Guide to Pharmacology 710 Link_out
HET SPM Link_out
Wikipedia http://en.wikipedia.org/wiki/Spermine Link_out
ATC Codes Not Available
AHFS Codes Not Available
PDB Entries
FDA label Not Available
MSDS show (19.4 KB)
Interactions
Drug Interactions Not Available
Food Interactions Not Available
Targets

1. Spermine synthase

Pharmacological action: yes
Actions: ligand

S-adenosylmethioninamine + spermidine = 5'- methylthioadenosine + spermine

Organism class: human
UniProt ID: P52788 Link_out
Gene: SMS Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Lopatin AN, Shantz LM, Mackintosh CA, Nichols CG, Pegg AE: Modulation of potassium channels in the hearts of transgenic and mutant mice with altered polyamine biosynthesis. J Mol Cell Cardiol. 2000 Nov;32(11):2007-24. Pubmed
  2. Korhonen VP, Niiranen K, Halmekyto M, Pietila M, Diegelman P, Parkkinen JJ, Eloranta T, Porter CW, Alhonen L, Janne J: Spermine deficiency resulting from targeted disruption of the spermine synthase gene in embryonic stem cells leads to enhanced sensitivity to antiproliferative drugs. Mol Pharmacol. 2001 Feb;59(2):231-8. Pubmed
  3. Cason AL, Ikeguchi Y, Skinner C, Wood TC, Holden KR, Lubs HA, Martinez F, Simensen RJ, Stevenson RE, Pegg AE, Schwartz CE: X-linked spermine synthase gene (SMS) defect: the first polyamine deficiency syndrome. Eur J Hum Genet. 2003 Dec;11(12):937-44. Pubmed
  4. Wang X, Ikeguchi Y, McCloskey DE, Nelson P, Pegg AE: Spermine synthesis is required for normal viability, growth, and fertility in the mouse. J Biol Chem. 2004 Dec 3;279(49):51370-5. Epub 2004 Sep 30. Pubmed
  5. Schwartz CE, Wang X, Stevenson RE, Pegg AE: Spermine synthase deficiency resulting in x-linked intellectual disability (snyder-robinson syndrome). Methods Mol Biol. 2011;720:437-45. Pubmed
  6. Wang X, Pegg AE: Use of (gyro) gy and spermine synthase transgenic mice to study functions of spermine. Methods Mol Biol. 2011;720:159-70. Pubmed
  7. Theiss C, Bohley P, Voigt J: Regulation by polyamines of ornithine decarboxylase activity and cell division in the unicellular green alga Chlamydomonas reinhardtii. Plant Physiol. 2002 Apr;128(4):1470-9. Pubmed
  8. Krauss M, Langnaese K, Richter K, Brunk I, Wieske M, Ahnert-Hilger G, Veh RW, Laube G: Spermidine synthase is prominently expressed in the striatal patch compartment and in putative interneurones of the matrix compartment. J Neurochem. 2006 Apr;97(1):174-89. Epub 2006 Mar 3. Pubmed
  9. Kobayashi M, Takao K, Shiota Y, Sugita Y, Takahashi M, Nakae D, Samejima K: Inhibition of putrescine aminopropyltransferase influences rat liver regeneration. Biol Pharm Bull. 2006 May;29(5):863-7. Pubmed

2. Spermine oxidase

Pharmacological action: yes
Actions: ligand

Flavoenzyme which catalyzes the oxidation of spermine to spermidine. Can also use 1-N-acetylspermine and spermidine as substrates, with different affinity depending on the isoform (isozyme) and on the experimental conditions. Plays an important role in the regulation of polyamine intracellular concentration and has the potential to act as a determinant of cellular sensitivity to the antitumor polyamine analogs. May contribute to beta-alanine production via aldehyde dehydrogenase conversion of 3-amino-propanal

Organism class: human
UniProt ID: Q9NWM0 Link_out
Gene: SMOX Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Binda C, Angelini R, Federico R, Ascenzi P, Mattevi A: Structural bases for inhibitor binding and catalysis in polyamine oxidase. Biochemistry. 2001 Mar 6;40(9):2766-76. Pubmed
  2. Vujcic S, Diegelman P, Bacchi CJ, Kramer DL, Porter CW: Identification and characterization of a novel flavin-containing spermine oxidase of mammalian cell origin. Biochem J. 2002 Nov 1;367(Pt 3):665-75. Pubmed
  3. Vujcic S, Liang P, Diegelman P, Kramer DL, Porter CW: Genomic identification and biochemical characterization of the mammalian polyamine oxidase involved in polyamine back-conversion. Biochem J. 2003 Feb 15;370(Pt 1):19-28. Pubmed
  4. Wang Y, Murray-Stewart T, Devereux W, Hacker A, Frydman B, Woster PM, Casero RA Jr: Properties of purified recombinant human polyamine oxidase, PAOh1/SMO. Biochem Biophys Res Commun. 2003 May 16;304(4):605-11. Pubmed
  5. Bacchi CJ, Rattendi D, Faciane E, Yarlett N, Weiss LM, Frydman B, Woster P, Wei B, Marton LJ, Wittner M: Polyamine metabolism in a member of the phylum Microspora (Encephalitozoon cuniculi): effects of polyamine analogues. Microbiology. 2004 May;150(Pt 5):1215-24. Pubmed

3. DNA

Pharmacological action: yes
Actions: binder

DNA is the molecule of heredity, as it is responsible for the genetic propagation of most inherited traits. It is a polynucleic acid that carries genetic information on cell growth, division, and function. DNA consists of two long strands of nucleotides twisted into a double helix and held together by hydrogen bonds. The sequence of nucleotides determines hereditary characteristics. Each strand serves as the template for subsequent DNA replication and as a template for mRNA production, leading to protein synthesis via ribosomes.

Gene Sequence: FASTA

References:
  1. Trubetskoy VS, Wolff JA, Budker VG: The role of a microscopic colloidally stabilized phase in solubilizing oligoamine-condensed DNA complexes. Biophys J. 2003 Feb;84(2 Pt 1):1124-30. Pubmed
  2. Cho SK, Kwon YJ: Polyamine/DNA polyplexes with acid-degradable polymeric shell as structurally and functionally virus-mimicking nonviral vectors. J Control Release. 2010 Dec 16. Pubmed
  3. Saminathan M, Thomas T, Shirahata A, Pillai CK, Thomas TJ: Polyamine structural effects on the induction and stabilization of liquid crystalline DNA: potential applications to DNA packaging, gene therapy and polyamine therapeutics. Nucleic Acids Res. 2002 Sep 1;30(17):3722-31. Pubmed

4. Ornithine decarboxylase

Pharmacological action: unknown
Actions: product of
Organism class: human
UniProt ID: P11926 Link_out
Gene: ODC1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Nilsson J, Grahn B, Heby O: Antizyme inhibitor is rapidly induced in growth-stimulated mouse fibroblasts and releases ornithine decarboxylase from antizyme suppression. Biochem J. 2000 Mar 15;346 Pt 3:699-704. Pubmed
  2. Ray RM, Viar MJ, Yuan Q, Johnson LR: Polyamine depletion delays apoptosis of rat intestinal epithelial cells. Am J Physiol Cell Physiol. 2000 Mar;278(3):C480-9. Pubmed
  3. Korhonen VP, Niiranen K, Halmekyto M, Pietila M, Diegelman P, Parkkinen JJ, Eloranta T, Porter CW, Alhonen L, Janne J: Spermine deficiency resulting from targeted disruption of the spermine synthase gene in embryonic stem cells leads to enhanced sensitivity to antiproliferative drugs. Mol Pharmacol. 2001 Feb;59(2):231-8. Pubmed
  4. Rohn G, Els T, Hell K, Ernestus RI: Regional distribution of ornithine decarboxylase activity and polyamine levels in experimental cat brain tumors. Neurochem Int. 2001 Aug;39(2):135-40. Pubmed
  5. Ernestus RI, Rohn G, Schroder R, Els T, Klekner A, Paschen W, Klug N: Polyamine metabolism in brain tumours: diagnostic relevance of quantitative biochemistry. J Neurol Neurosurg Psychiatry. 2001 Jul;71(1):88-92. Pubmed
  6. Lee NK, Maclean HE: Polyamines, androgens and skeletal muscle hypertrophy. J Cell Physiol. 2010 Dec 7. Pubmed
Enzymes

1. Xanthine dehydrogenase/oxidase

Actions: inhibitor

This enzyme can be converted from the dehydrogenase form (D) to the oxidase form (O) irreversibly by proteolysis or reversibly through the oxidation of sulfhydryl groups

UniProt ID: P47989 Link_out
Gene: XDH Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Lovaas E, Carlin G: Spermine: an anti-oxidant and anti-inflammatory agent. Free Radic Biol Med. 1991;11(5):455-61. Pubmed

2. Diamine acetyltransferase 1

Actions: substrate

Enzyme which catalyzes the acetylation of polyamines. Substrate specificity:norspermidine = spermidine >> spermine > 1- N-acetylspermine > putrescine. This highly regulated enzyme allows a fine attenuation of the intracellular concentration of polyamines. Also involved in the regulation of polyamine transport out of cells

UniProt ID: P21673 Link_out
Gene: SAT1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Vujcic S, Halmekyto M, Diegelman P, Gan G, Kramer DL, Janne J, Porter CW: Effects of conditional overexpression of spermidine/spermine N1-acetyltransferase on polyamine pool dynamics, cell growth, and sensitivity to polyamine analogs. J Biol Chem. 2000 Dec 8;275(49):38319-28. Pubmed
  2. Hegardt C, Andersson G, Oredsson SM: Changes in polyamine metabolism during glucocorticoid-induced programmed cell death in mouse thymus. Cell Biol Int. 2000;24(12):871-80. Pubmed
  3. Marverti G, Bettuzzi S, Astancolle S, Pinna C, Monti MG, Moruzzi MS: Differential induction of spermidine/spermine N1-acetyltransferase activity in cisplatin-sensitive and -resistant ovarian cancer cells in response to N1,N12-bis(ethyl)spermine involves transcriptional and post-transcriptional regulation. Eur J Cancer. 2001 Jan;37(2):281-9. Pubmed
  4. Scorcioni F, Corti A, Davalli P, Astancolle S, Bettuzzi S: Manipulation of the expression of regulatory genes of polyamine metabolism results in specific alterations of the cell-cycle progression. Biochem J. 2001 Feb 15;354(Pt 1):217-23. Pubmed
  5. Min SH, Simmen RC, Alhonen L, Halmekyto M, Porter CW, Janne J, Simmen FA: Altered levels of growth-related and novel gene transcripts in reproductive and other tissues of female mice overexpressing spermidine/spermine N1-acetyltransferase (SSAT). J Biol Chem. 2002 Feb 1;277(5):3647-57. Epub 2001 Nov 14. Pubmed
  6. Limsuwun K, Jones PG: Spermidine acetyltransferase is required to prevent spermidine toxicity at low temperatures in Escherichia coli. J Bacteriol. 2000 Oct;182(19):5373-80. Pubmed

3. Diamine acetyltransferase 2

Actions: substrate

Enzyme which catalyzes the acetylation of polyamines. Substrate specificity:norspermidine > spermidine = spermine >> N(1)acetylspermine = putrescine

UniProt ID: Q96F10 Link_out
Gene: SAT2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Chen Y, Vujcic S, Liang P, Diegelman P, Kramer DL, Porter CW: Genomic identification and biochemical characterization of a second spermidine/spermine N1-acetyltransferase. Biochem J. 2003 Aug 1;373(Pt 3):661-7. Pubmed
  2. Coleman CS, Stanley BA, Jones AD, Pegg AE: Spermidine/spermine-N1-acetyltransferase-2 (SSAT2) acetylates thialysine and is not involved in polyamine metabolism. Biochem J. 2004 Nov 15;384(Pt 1):139-48. Pubmed
  3. Vogel NL, Boeke M, Ashburner BP: Spermidine/Spermine N1-Acetyltransferase 2 (SSAT2) functions as a coactivator for NF-kappaB and cooperates with CBP and P/CAF to enhance NF-kappaB-dependent transcription. Biochim Biophys Acta. 2006 Oct;1759(10):470-7. Epub 2006 Aug 30. Pubmed
  4. Limsuwun K, Jones PG: Spermidine acetyltransferase is required to prevent spermidine toxicity at low temperatures in Escherichia coli. J Bacteriol. 2000 Oct;182(19):5373-80. Pubmed
Transporters

1. Organic cation/carnitine transporter 1

Actions: inhibitor

Sodium-ion dependent, low affinity carnitine transporter. Probably transports one sodium ion with one molecule of carnitine. Also transports organic cations such as tetraethylammonium (TEA) without the involvement of sodium. Relative uptake activity ratio of carnitine to TEA is 1.78. A key substrate of this transporter seems to be ergothioneine (ET)

UniProt ID: Q9H015 Link_out
Gene: SLC22A4 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Yabuuchi H, Tamai I, Nezu J, Sakamoto K, Oku A, Shimane M, Sai Y, Tsuji A: Novel membrane transporter OCTN1 mediates multispecific, bidirectional, and pH-dependent transport of organic cations. J Pharmacol Exp Ther. 1999 May;289(2):768-73. Pubmed

2. Solute carrier family 22 member 1

Actions: substrate

Translocates a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnicotinamide (NMN), 4-(4-(dimethylamino)styryl)- N-methylpyridinium (ASP), the endogenous compounds choline, guanidine, histamine, epinephrine, adrenaline, noradrenaline and dopamine, and the drugs quinine, and metformin. The transport of organic cations is inhibited by a broad array of compounds like tetramethylammonium (TMA), cocaine, lidocaine, NMDA receptor antagonists, atropine, prazosin, cimetidine, TEA and NMN, guanidine, cimetidine, choline, procainamide, quinine, tetrabutylammonium, and tetrapentylammonium. Translocates organic cations in an electrogenic and pH-independent manner. Translocates organic cations across the plasma membrane in both directions. Transports the polyamines spermine and spermidine. Transports pramipexole across the basolateral membrane of the proximal tubular epithelial cells. The choline transport is activated by MMTS. Regulated by various intracellular signaling pathways including inhibition by protein kinase A activation, and endogenously activation by the calmodulin complex, the calmodulin- dependent kinase II and LCK tyrosine kinase

UniProt ID: O15245 Link_out
Gene: SLC22A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Busch AE, Quester S, Ulzheimer JC, Waldegger S, Gorboulev V, Arndt P, Lang F, Koepsell H: Electrogenic properties and substrate specificity of the polyspecific rat cation transporter rOCT1. J Biol Chem. 1996 Dec 20;271(51):32599-604. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19