A polyamine is an

organic compound Some chemical authorities define an organic compound as a chemical compound that contains a carbon–hydrogen or carbon–carbon bond; others consider an organic compound to be any chemical compound that contains carbon. For example, carbon-co ...

having two or more

amino group In chemistry, amines (, ) are organic compounds that contain carbon-nitrogen bonds. Amines are formed when one or more hydrogen atoms in ammonia are replaced by alkyl or aryl groups. The nitrogen atom in an amine possesses a lone pair of elec ...

s. Alkyl polyamines occur naturally, but some are synthetic. Alkylpolyamines are colorless,

hygroscopic Hygroscopy is the phenomenon of attracting and holding water molecules via either absorption (chemistry), absorption or adsorption from the surrounding Natural environment, environment, which is usually at normal or room temperature. If water mol ...

, and water soluble. Near neutral pH, they exist as the ammonium derivatives. Most

aromatic In organic chemistry, aromaticity is a chemical property describing the way in which a conjugated system, conjugated ring of unsaturated bonds, lone pairs, or empty orbitals exhibits a stabilization stronger than would be expected from conjugati ...

polyamines are crystalline solids at room temperature.

Natural polyamines

Low-molecular-weight linear polyamines are found in all forms of life. The principal examples are the triamine

spermidine Spermidine is a polyamine compound () found in ribosomes and living tissues and having various metabolic functions within organisms. Function Spermidine is an Aliphatic compound, aliphatic polyamine. Spermidine synthase (SPDS) catalyzes its form ...

and the tetraamine

spermine Spermine is a polyamine involved in cellular metabolism that is found in all eukaryotic cells. The precursor for synthesis of spermine is the amino acid ornithine. It is an essential growth factor in some bacteria as well. It is found as a p ...

. They are structurally and biosynthetically related to the diamines

putrescine Putrescine is an organic compound with the formula (CH2)4(NH2)2. It is a colorless solid that melts near room temperature. It is classified as a diamine. Together with cadaverine, it is largely responsible for the foul odor of Putrefaction, putref ...

and

cadaverine Cadaverine is an organic compound with the formula (CH2)5(NH2)2. Classified as a diamine, it is a colorless liquid with an unpleasant odor. It is present in small quantities in living organisms but is often associated with the putrefaction of Tiss ...

. Polyamine metabolism is regulated by the activity of the enzyme

ornithine decarboxylase The enzyme ornithine decarboxylase (, ODC) catalyzes the decarboxylation of ornithine (a product of the urea cycle) to form putrescine. This reaction is the committed step in polyamine synthesis. In humans, this protein has 461 amino acids ...

(ODC). Polyamines are found in high concentrations in the

mammal A mammal () is a vertebrate animal of the Class (biology), class Mammalia (). Mammals are characterised by the presence of milk-producing mammary glands for feeding their young, a broad neocortex region of the brain, fur or hair, and three ...

ian

brain The brain is an organ (biology), organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It consists of nervous tissue and is typically located in the head (cephalization), usually near organs for ...

. File:Spermidine-2D-skeletal.svg,

File:Spermine.svg,

Synthetic polyamines

Ethyleneamines are a commercially-important class of synthetic polyamines with ethylene ( linkages); global production capacity was estimated at 385,000 tonnes in 2001. They are chemical intermediates often used to make surfactants and as crosslinkers for

epoxy Epoxy is the family of basic components or Curing (chemistry), cured end products of epoxy Resin, resins. Epoxy resins, also known as polyepoxides, are a class of reactive prepolymers and polymers which contain epoxide groups. The epoxide fun ...

resins. Some members of this class include: *

Ethylenediamine Ethylenediamine (abbreviated as en when a ligand) is the organic compound with the formula C2H4(NH2)2. This colorless liquid with an ammonia-like odor is a basic amine. It is a widely used building block in chemical synthesis, with approximately ...

, first member of this series. It is a chelating ligand by itself, and it is a precursor to the popular metal sequestrant,

EDTA Ethylenediaminetetraacetic acid (EDTA), also called EDTA acid, is an aminopolycarboxylic acid with the formula . This white, slightly water-soluble solid is widely used to bind to iron (Fe2+/Fe3+) and calcium ions (Ca2+), forming water-solubl ...

(ethylenediaminetetraacetic acid). Permethylated, ethylenediamine yields

tetramethylethylenediamine Tetramethylethylenediamine (TMEDA or TEMED) is a chemical compound with the formula (CH3)2NCH2CH2N(CH3)2. This species is derived from ethylenediamine by replacement of the four amine hydrogens with four methyl groups. It is a colorless liquid, ...

(TMEDA) that has a very high affinity for lithium ions. *

Macrocyclic Macrocycles are often described as molecules and ions containing a ring of twelve or more atoms. Classical examples include the crown ethers, calixarenes, porphyrins, and cyclodextrins. Macrocycles describe a large, mature area of chemistry. ...

polyamines analogous to

crown ethers In organic chemistry, crown ethers are cyclic chemical compounds that consist of a ring containing several ether groups (). The most common crown ethers are cyclic oligomers of ethylene oxide, the repeating unit being ethyleneoxy, i.e., . Impor ...

1,4,7-triazacyclononane 1,4,7-Triazacyclononane, known as "TACN" which is pronounced "tack-en," is an aza-crown ether with the formula (C2H4NH)3. TACN is derived, formally speaking, from cyclononane by replacing three equidistant CH2 groups with NH groups. TACN is one o ...

() and

cyclen Cyclen (1,4,7,10-tetraazacyclododecane) is an aza-crown ether with the formula (CH2CH2NH)4. It is a white solid. It forms Coordination complex, coordination complexes with metal cations and is used to synthesize the chelating agent DOTA (chelator) ...

(). A related tetraaza macrocycle is

cyclam Cyclam (1,4,8,11-tetraazacyclotetradecane) is an organic compound with the formula (NHCH2CH2NHCH2CH2CH2)2. Classified as an aza-crown ether, it is a white solid that is soluble in water. As a macrocyclic ligand, it binds strongly to many transit ...

. *

Tris(2-aminoethyl)amine Tris(2-aminoethyl)amine is the organic compound with the chemical formula, formula N(CH2CH2NH2)3. This colourless liquid is soluble in water and is highly basic, consisting of a tertiary amine center and three pendant primary amine groups. Tris(2- ...

() is a branched polyamine that is a minor side product of the

polyethyleneamine Ethyleneamines are a class of amine compounds containing ethylene (-CH2CH2-) linkages between amine groups. These compounds are generally colorless, low-viscosity liquids with a fishy amine odor. They are primarily used as building block chemicals ...

process. A related tripodal polyamine is

1,1,1-tris(aminomethyl)ethane 1,1,1-Tris(aminomethyl)ethane (TAME) is an organic compound with the formula CHC(CHNH). It is a colorless liquid. It is classified as a polyamine tripodal ligand, i.e., capable of binding to metal ions through three sites and hence is a tridentat ...

. These are chelating ligands. *

Polyethylenimine Polyethylenimine (PEI) or polyaziridine is a polymer with repeating units composed of the amine group and two carbon Aliphatic_compound, aliphatic ''CHCH'' spacers. Linear polyethyleneimines contain all Amines#Classification_of_amines, secondary ...

is a

polymer A polymer () is a chemical substance, substance or material that consists of very large molecules, or macromolecules, that are constituted by many repeat unit, repeating subunits derived from one or more species of monomers. Due to their br ...

derived from

aziridine Aziridine is an organic compound consisting of the three-membered heterocycle . It is a colorless, toxic, volatile liquid that is of significant practical interest. Aziridine was discovered in 1888 by the chemist Siegmund Gabriel. Its deriva ...

. Other synthetic polyamines include

1,3,5-triazinane Triazinanes are a class of nitrogen-containing heterocycles.''Heterocyclic Chemistry'' T.L. Gilchrist 1985 (1997, The parent molecules' molecular formula is . They exist in three isomeric forms, 1,3,5-triazinanes being common. The triazinan ...

(not to be confused with 1,3,5-triazine) and N-substituted analogs. The methylene () linkages are derived from

formaldehyde Formaldehyde ( , ) (systematic name methanal) is an organic compound with the chemical formula and structure , more precisely . The compound is a pungent, colourless gas that polymerises spontaneously into paraformaldehyde. It is stored as ...

. The reaction product of monoethanolamine and formaldehyde is known industrially as "MEA triazine" (it is actually a triazinane), and it serves as a water-soluble

hydrogen sulfide Hydrogen sulfide is a chemical compound with the formula . It is a colorless chalcogen-hydride gas, and is toxic, corrosive, and flammable. Trace amounts in ambient atmosphere have a characteristic foul odor of rotten eggs. Swedish chemist ...

scavenger.

Hexamethylenetetramine Hexamethylenetetramine (HMTA), also known as 1,3,5,7-tetraazaadamantane, is a heterocyclic organic compound with diverse applications. It has the chemical formula (CH2)6N4 and is a white crystalline compound that is highly soluble in water and p ...

(hexamine) is another product of formaldehyde and ammonia that has various uses in industry. Domestically, it is used as a solid camping fuel. In the laboratory, it reacts with

alkyl halides The haloalkanes (also known as halogenoalkanes or alkyl halides) are alkanes containing one or more halogen substituents of hydrogen atom. They are a subset of the general class of halocarbons, although the distinction is not often made. Haloalka ...

to selectively prepare primary amines in the

Delépine reaction The Delépine reaction is the organic synthesis of primary amines (4) by reaction of benzyl or alkyl halides (1) with hexamethylenetetramine (2) followed by acid hydrolysis of the quaternary ammonium salt (3). It is named after the French chemist S ...

. File:Tris(2-aminoethyl)amine.svg,

File:Cyclen.svg,

Cyclen Cyclen (1,4,7,10-tetraazacyclododecane) is an aza-crown ether with the formula (CH2CH2NH)4. It is a white solid. It forms Coordination complex, coordination complexes with metal cations and is used to synthesize the chelating agent DOTA (chelator) ...

File:1,4,7-triazacyclononane.svg,

1,4,7-Triazacyclononane 1,4,7-Triazacyclononane, known as "TACN" which is pronounced "tack-en," is an aza-crown ether with the formula (C2H4NH)3. TACN is derived, formally speaking, from cyclononane by replacing three equidistant CH2 groups with NH groups. TACN is one o ...

File:1,1,1-Tris(aminomethyl)ethane.svg,

1,1,1-Tris(aminomethyl)ethane 1,1,1-Tris(aminomethyl)ethane (TAME) is an organic compound with the formula CHC(CHNH). It is a colorless liquid. It is classified as a polyamine tripodal ligand, i.e., capable of binding to metal ions through three sites and hence is a tridentat ...

File:Branched PEI.png, Subunit of

polyethylenimine Polyethylenimine (PEI) or polyaziridine is a polymer with repeating units composed of the amine group and two carbon Aliphatic_compound, aliphatic ''CHCH'' spacers. Linear polyethyleneimines contain all Amines#Classification_of_amines, secondary ...

File:Hexamine.svg,

with its

adamantane Adamantane is an organic compound with formula C10H16 or, more descriptively, (CH)4(CH2)6. Adamantane molecules can be described as the fusion of three cyclohexane rings. The molecule is both rigid and virtually stress-free. Adamantane is the mo ...

-type structure

Biological function

Although it is known that the biosynthesis of polyamines is highly regulated, the biological function of polyamines is only partly understood. In their cationic ammonium form, they bind to

DNA Deoxyribonucleic acid (; DNA) is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of al ...

, and, in structure, they represent compounds with cations that are found at ''regularly spaced intervals'' (in contrast to or , which are point charges). They have also been found to act as promoters of programmed ribosomal frameshifting during translation. Inhibition of polyamine biosynthesis retards or stops

cell growth Cell most often refers to: * Cell (biology), the functional basic unit of life * Cellphone, a phone connected to a cellular network * Clandestine cell, a penetration-resistant form of a secret or outlawed organization * Electrochemical cell, a de ...

. The provision of exogenous polyamines restores the growth of these cells. Most eukaryotic cells express a polyamine-transporting ATPase on their

cell membrane The cell membrane (also known as the plasma membrane or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of a cell from the outside environment (the extr ...

that facilitates the internalization of exogenous polyamines. This system is highly active in rapidly proliferating cells and is the target of some chemotherapeutics currently under development. Polyamines are also modulators of a variety of

ion channel Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by Gating (electrophysiol ...

s, including

NMDA receptor The ''N''-methyl-D-aspartate receptor (also known as the NMDA receptor or NMDAR), is a glutamate receptor and predominantly Ca2+ ion channel found in neurons. The NMDA receptor is one of three types of ionotropic glutamate receptors, the other ...

s and

AMPA receptor The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA receptor, AMPAR, or quisqualate receptor) is an ionotropic receptor, ionotropic glutamate receptor (iGluR) and predominantly sodium ion channel that mediates fast excitator ...

s. They block

inward-rectifier potassium channel Inward-rectifier potassium channels (Kir, IRK) are a specific Lipid-gated_ion_channels, lipid-gated subset of potassium channels. To date, seven subfamilies have been identified in various mammalian cell types, plants, and bacteria. They are acti ...

s so that the currents of the channels are inwardly rectified, thereby the cellular energy, i.e. ion gradient across the cell membrane, is conserved. In addition, polyamine participate in initiating the expression of SOS response of Colicin E7 operon and down-regulate proteins that are essential for colicin E7 uptake, thus conferring a survival advantage on colicin-producing ''E. coli'' under stress conditions. Polyamines can enhance the permeability of the

blood–brain barrier The blood–brain barrier (BBB) is a highly selective semipermeable membrane, semipermeable border of endothelium, endothelial cells that regulates the transfer of solutes and chemicals between the circulatory system and the central nervous system ...

. They are involved in modulating

senescence Senescence () or biological aging is the gradual deterioration of Function (biology), functional characteristics in living organisms. Whole organism senescence involves an increase in mortality rate, death rates or a decrease in fecundity with ...

of organs in plants and are therefore considered as a

plant hormone Plant hormones (or phytohormones) are signal molecules, produced within plants, that occur in extremely low concentrations. Plant hormones control all aspects of plant growth and development, including embryogenesis, the regulation of Organ (anat ...

. In addition, they are directly involved in regulation of programmed cell death.

Homology-directed DNA repair

Polyamines promote

homologous recombination Homologous recombination is a type of genetic recombination in which genetic information is exchanged between two similar or identical molecules of double-stranded or single-stranded nucleic acids (usually DNA as in Cell (biology), cellular organi ...

(HR)-mediated double-strand break (DSB) repair. Polyamines enhance the DNA strand exchange activity of

RAD51 DNA repair protein RAD51 homolog 1 is a protein encoded by the gene ''RAD51''. The enzyme encoded by this gene is a member of the RAD51 protein family which assists in repair of DNA double strand breaks. RAD51 family members are homologous to t ...

recombinase Recombinases are genetic recombination enzymes. Site specific recombinases DNA recombinases are widely used in multicellular organisms to manipulate the structure of genomes, and to control gene expression. These enzymes, derived from bacteria ( ...

. Depletion of polyamines sensitizes cells to genotoxic substances such as

ionizing radiation Ionizing (ionising) radiation, including Radioactive decay, nuclear radiation, consists of subatomic particles or electromagnetic waves that have enough energy per individual photon or particle to ionization, ionize atoms or molecules by detaching ...

and

ultraviolet Ultraviolet radiation, also known as simply UV, is electromagnetic radiation of wavelengths of 10–400 nanometers, shorter than that of visible light, but longer than X-rays. UV radiation is present in sunlight and constitutes about 10% of ...

radiation. The effect of polyamines on RAD51 arises from their ability to enhance the capture of homologous duplex DNA and promote RAD-51-mediated homologous DNA pairing and exchange activity. Polyamines appear to have an evolutionarily conserved role in regulating recombinase activity.

Biosynthesis of spermidine, spermine, thermospermine

Spermidine Spermidine is a polyamine compound () found in ribosomes and living tissues and having various metabolic functions within organisms. Function Spermidine is an Aliphatic compound, aliphatic polyamine. Spermidine synthase (SPDS) catalyzes its form ...

is synthesized from putrescine, using an aminopropyl group from decarboxylated ''S''-adenosyl-L-methionine (SAM), ''S''-Adenosylmethioninamine. The reaction is catalyzed by

spermidine synthase Spermidine synthase is an enzyme () that catalyzes the transfer of the propylamine group from ''S''-adenosylmethioninamine to putrescine in the biosynthesis of spermidine. The systematic name is S-adenosyl 3-(methylthio)propylamine:putrescine 3- ...

Spermine Spermine is a polyamine involved in cellular metabolism that is found in all eukaryotic cells. The precursor for synthesis of spermine is the amino acid ornithine. It is an essential growth factor in some bacteria as well. It is found as a p ...

is synthesized from the reaction of spermidine with SAM in the presence of the enzyme

spermine synthase Spermine synthase (, ''spermidine aminopropyltransferase'', ''spermine synthetase'') is an enzyme that converts spermidine into spermine. This enzyme catalyses the following chemical reaction : S-adenosylmethioninamine + spermidine \rightleftha ...

. The polyamines undergo rapid interconversion in the polyamine cycle, in which putrescine leads to synthesis of spermidine and spermine, with degradation of these polyamines to form putrescine, which can begin the cycle again. Thermospermine () is a structural

isomer In chemistry, isomers are molecules or polyatomic ions with identical molecular formula – that is, the same number of atoms of each element (chemistry), element – but distinct arrangements of atoms in space. ''Isomerism'' refers to the exi ...

of spermine and a plant growth regulator. It is produced from spermidine by the action of

thermospermine synthase Thermospermine synthase (, ''TSPMS'', ''ACL5'' (''ACAULIS5''), ''SAC51'') is an enzyme with systematic name ''S-adenosylmethioninamine:spermidine 3-aminopropyltransferase (thermospermine synthesizing)''. This enzyme catalyses the following chemica ...

, which is encoded by a gene named ACAULIS5 (ACL5).

Polyamine analogues

The critical role of polyamines in cell growth has led to the development of a number of agents that interfere with polyamine metabolism. These agents are used in

cancer therapy Cancer treatments are a wide range of treatments available for the many different types of cancer, with each cancer type needing its own specific treatment. Treatments can include surgery, chemotherapy, radiation therapy, hormonal therapy, targe ...

. Polyamine analogues upregulate

p53 p53, also known as tumor protein p53, cellular tumor antigen p53 (UniProt name), or transformation-related protein 53 (TRP53) is a regulatory transcription factor protein that is often mutated in human cancers. The p53 proteins (originally thou ...

in a cell leading to restriction of proliferation and

apoptosis Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biol ...

. It also decreases the expression of estrogen receptor alpha in ER-positive breast cancer.

References

External links

Polyamines in cell cycle proliferation and cell death
* Extensive review of literature through 2001 on polyamine structure, properties, metabolism in mammals, and physiological and pathophysiological roles (See article Table of Contents) {{Authority control Plant hormones