SynCED: Spermine

Record Information

Version

1.0

Creation Date

2014-08-29 05:48:38 UTC

Update Date

2026-05-14 16:24:07 UTC

Accession Number

CHEM003126

Identification

Common Name

Spermine

Class

Small Molecule

Description

Spermine is a uremic toxin. Uremic toxins can be subdivided into three major groups based upon their chemical and physical characteristics: 1) small, water-soluble, non-protein-bound compounds, such as urea; 2) small, lipid-soluble and/or protein-bound compounds, such as the phenols and 3) larger so-called middle-molecules, such as beta2-microglobulin. Chronic exposure of uremic toxins can lead to a number of conditions including renal damage, chronic kidney disease and cardiovascular disease. Spermine is associated with nucleic acids, particularly in viruses, and is thought to stabilize the helical structure. [PubChem]

Contaminant Sources

FooDB Chemicals
HMDB Contaminants - Feces
HMDB Contaminants - Urine
HPV EPA Chemicals
T3DB toxins

Contaminant Type

Amine
Dietary Supplement
Drug
Food Toxin
Metabolite
Micronutrient
Natural Compound
Nutraceutical
Organic Compound
Supplement
Uremic Toxin

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Value	Source
4,9-Diaza-1,12-dodecanediamine	ChEBI
4,9-Diazadodecane-1,12-diamine	ChEBI
N,N'-bis(3-aminopropyl)-1,4-butanediamine	ChEBI
1,5,10,14-Tetraazatetradecane	HMDB
4,9-Diazadodecamethylenediamine	HMDB
Diaminopropyl-tetramethylenediamine	HMDB
Diaminopropyltetramethylenediamine	HMDB
Gerontine	HMDB
Musculamine	HMDB
N,N'-bis(3-aminopropyl)-1,4-tetramethylenediamine	HMDB
N,N'-bis(3-aminopropyl)butane-1,4-diamine	HMDB
N1,N4-Bis(3-aminopropyl)-1,4-butanediamine	HMDB
Neuridine	HMDB
Spermin	HMDB
Spermine dihydrate	HMDB
Spermine puriss	HMDB
SPM	HMDB

Chemical Formula

C₁₀H₂₆N₄

Average Molecular Mass

202.340 g/mol

Monoisotopic Mass

202.216 g/mol

CAS Registry Number

71-44-3

IUPAC Name

(3-aminopropyl)({4-[(3-aminopropyl)amino]butyl})amine

Traditional Name

spermine

SMILES

NCCCNCCCCNCCCN

InChI Identifier

InChI=1S/C10H26N4/c11-5-3-9-13-7-1-2-8-14-10-4-6-12/h13-14H,1-12H2

InChI Key

PFNFFQXMRSDOHW-UHFFFAOYSA-N

Chemical Taxonomy

Description

Belongs to the class of organic compounds known as dialkylamines. These are organic compounds containing a dialkylamine group, characterized by two alkyl groups bonded to the amino nitrogen.

Kingdom

Organic compounds

Super Class

Organic nitrogen compounds

Class

Organonitrogen compounds

Sub Class

Amines

Direct Parent

Dialkylamines

Alternative Parents

Substituents

Secondary aliphatic amine
Organopnictogen compound
Hydrocarbon derivative
Primary amine
Primary aliphatic amine
Aliphatic acyclic compound

Molecular Framework

Aliphatic acyclic compounds

External Descriptors

tetraamine (CHEBI:15746 )
polyazaalkane (CHEBI:15746 )

Biological Properties

Status

Detected and Not Quantified

Origin

Endogenous

Cellular Locations

Cytoplasm
Extracellular

Biofluid Locations

Not Available

Tissue Locations

Brain
Erythrocyte
Fibroblasts
Intestine
Liver
Muscle
Neuron
Pancreas
Platelet
Prostate
Skin
Testes

Pathways

Name	SMPDB Link	KEGG Link
Spermidine and Spermine Biosynthesis	SMP00445	Not Available

Applications

immunosuppressive agent

Biological Roles

Chemical Roles

antioxidant

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	29°C
Boiling Point	150-150°C
Solubility	> 100 mg/mL

Predicted Properties

Property	Value	Source
Water Solubility	2.19 g/L	ALOGPS
logP	-0.66	ALOGPS
logP	-1.5	ChemAxon
logS	-2	ALOGPS
pKa (Strongest Basic)	10.8	ChemAxon
Physiological Charge	4	ChemAxon
Hydrogen Acceptor Count	4	ChemAxon
Hydrogen Donor Count	4	ChemAxon
Polar Surface Area	76.1 Å²	ChemAxon
Rotatable Bond Count	11	ChemAxon
Refractivity	62.56 m³·mol⁻¹	ChemAxon
Polarizability	26.69 Å³	ChemAxon
Number of Rings	0	ChemAxon
Bioavailability	Yes	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	No	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	No	ChemAxon

Spectra

Toxicity Profile

Route of Exposure

Endogenous, Ingestion, Dermal (contact)

Mechanism of Toxicity

Uremic toxins such as spermine are actively transported into the kidneys via organic ion transporters (especially OAT3). Increased levels of uremic toxins can stimulate the production of reactive oxygen species. This seems to be mediated by the direct binding or inhibition by uremic toxins of the enzyme NADPH oxidase (especially NOX4 which is abundant in the kidneys and heart) (3). Reactive oxygen species can induce several different DNA methyltransferases (DNMTs) which are involved in the silencing of a protein known as KLOTHO. KLOTHO has been identified as having important roles in anti-aging, mineral metabolism, and vitamin D metabolism. A number of studies have indicated that KLOTHO mRNA and protein levels are reduced during acute or chronic kidney diseases in response to high local levels of reactive oxygen species (4). 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.

Metabolism

Uremic toxins tend to accumulate in the blood either through dietary excess or through poor filtration by the kidneys. Most uremic toxins are metabolic waste products and are normally excreted in the urine or feces.

Toxicity Values

Not Available

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

No indication of carcinogenicity to humans (not listed by IARC).

Uses/Sources

For nutritional supplementation, also for treating dietary shortage or imbalance

Minimum Risk Level

Not Available

Health Effects

Chronic exposure to uremic toxins can lead to a number of conditions including renal damage, chronic kidney disease and cardiovascular disease.

Symptoms

As a uremic toxin, this compound can cause uremic syndrome. Uremic syndrome may affect any part of the body and can cause nausea, vomiting, loss of appetite, and weight loss. It can also cause changes in mental status, such as confusion, reduced awareness, agitation, psychosis, seizures, and coma. Abnormal bleeding, such as bleeding spontaneously or profusely from a very minor injury can also occur. Heart problems, such as an irregular heartbeat, inflammation in the sac that surrounds the heart (pericarditis), and increased pressure on the heart can be seen in patients with uremic syndrome. Shortness of breath from fluid buildup in the space between the lungs and the chest wall (pleural effusion) can also be present.

Treatment

Kidney dialysis is usually needed to relieve the symptoms of uremic syndrome until normal kidney function can be restored.

Concentrations

Not Available

External Links

DrugBank ID

DB00127

HMDB ID

HMDB0001256

FooDB ID

FDB003225

Phenol Explorer ID

Not Available

KNApSAcK ID

BiGG ID

BioCyc ID

METLIN ID

PDB ID

Not Available

Wikipedia Link

Chemspider ID

ChEBI ID

PubChem Compound ID

Kegg Compound ID

YMDB ID

ECMDB ID

References

Synthesis Reference

Koji Nakanishi, Amira T. Eldefrawi, Mohyee E. Eldefrawi, Peter N. R. Usherwood, “Butyryl-tyrosinyl spermine, analogs thereof and methods of preparing and using same.” U.S. Patent US5770625, issued January, 1966.

MSDS

Link

General References

1. Wrede, Fritz; Strack, Erich; Hettche, Otto. Spermine. VII. Z. physiol. Chem. (1928), 173 61-8.

2. Motyl T, Ploszaj T, Wojtasik A, Kukulska W, Podgurniak M: Polyamines in cow's and sow's milk. Comp Biochem Physiol B Biochem Mol Biol. 1995 Jul;111(3):427-33.

3. Wrede, Fritz; Strack, Erich; Hettche, Otto. Spermine. VII. Z. physiol. Chem. (1928), 173 61-8.

4. Mollica F, Li Volti S, Rapisarda A, Longo G, Pavone L, Vanella A: Increased erythrocytic spermine in Duchenne muscular dystrophy. Pediatr Res. 1980 Nov;14(11):1196-8.

5. Swift TA, Dias JA: Effects of the polyamine spermine on binding of follicle-stimulating hormone to membrane-bound immature bovine testis receptors. Biochim Biophys Acta. 1986 Feb 21;885(2):221-30.

6. Cipolla BG, Ziade J, Bansard JY, Moulinoux JP, Staerman F, Quemener V, Lobel B, Guille F: Pretherapeutic erythrocyte polyamine spermine levels discriminate high risk relapsing patients with M1 prostate carcinoma. Cancer. 1996 Sep 1;78(5):1055-65.

7. 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.

8. 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.

9. Jensen PK, Therkelsen AJ: Selective inhibition of fibroblasts by spermine in primary cultures of normal human skin epithelial cells. In Vitro. 1982 Oct;18(10):867-71.