A polyamine is an
organic compound
In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other carbon atoms), millions of organic compounds are known. The ...
having more than two
amino group
In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituent such ...
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 or adsorption from the surrounding environment, which is usually at normal or room temperature. If water molecules become suspended among the substance ...
, and water soluble. Near neutral pH, they exist as the ammonium derivatives.
Most
aromatic
In chemistry, aromaticity is a chemical property of cyclic ( ring-shaped), ''typically'' planar (flat) molecular structures with pi bonds in resonance (those containing delocalized electrons) that gives increased stability compared to satur ...
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. It was originally isolated from semen.
Function
Spermidine is an aliphatic polyamine. Spermidine synthase (SP ...
and the tetraamine
spermine
Spermine is a polyamine involved in cellular metabolism that is found in all Eukaryote, eukaryotic cells. The precursor for synthesis of spermine is the amino acid ornithine. It is an essential growth factor in some Bacterium, bacteria as well. ...
. 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 putrefying flesh, b ...
and
cadaverine
Cadaverine is an organic compound with the formula (CH2)5(NH2)2. Classified as 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 anim ...
. 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 and fo ...
(ODC).
Polyamines are found in high concentrations in the
mammal
Mammals () are a group of vertebrate animals constituting the class Mammalia (), characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fur or ...
ian
brain
A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a v ...
.
File:Spermidine-2D-skeletal.svg, spermidine
Spermidine is a polyamine compound () found in ribosomes and living tissues and having various metabolic functions within organisms. It was originally isolated from semen.
Function
Spermidine is an aliphatic polyamine. Spermidine synthase (SP ...
File:Spermine.svg, spermine
Spermine is a polyamine involved in cellular metabolism that is found in all Eukaryote, eukaryotic cells. The precursor for synthesis of spermine is the amino acid ornithine. It is an essential growth factor in some Bacterium, bacteria as well. ...
Synthetic polyamines
Several synthetic polyamines are used in
chemical industry
The chemical industry comprises the companies that produce industrial chemicals. Central to the modern world economy, it converts raw materials (oil, natural gas, air, water, metals, and minerals) into more than 70,000 different products. The ...
and the research laboratory. They are mainly of interest as additives to motor oil and as co-reactants (cold hardeners) with
epoxy
Epoxy is the family of basic components or cured end products of epoxy resins. Epoxy resins, also known as polyepoxides, are a class of reactive prepolymers and polymers which contain epoxide groups. The epoxide functional group is also coll ...
resins.
[
] Many synthetic polyamines feature NCH
2CH
2N linkages:
*
Diethylenetriamine
Diethylenetriamine (abbreviated and also known as 2,2’-Iminodi(ethylamine)) is an organic compound with the formula HN(CH2CH2NH2)2. This colourless hygroscopic liquid is soluble in water and polar organic solvents, but not simple hydrocarbons. ...
, abbreviated dien or DETA, (H
2N-CH
2CH
2-NH-CH
2CH
2-NH
2. The related permethylated derivative
pentamethyldiethylenetriamine is used as a chelating agent in
organolithium chemistry.
*
Triethylenetetramine
Triethylenetetramine (TETA and trien), also known as trientine (INN) when used medically, is an organic compound with the formula H2NHCH2CH2NH2sub>2. The pure freebase is a colorless oily liquid, but, like many amines, older samples assume a yell ...
(trien or TETA, H
2N-CH
2CH
2-NH-CH
2CH
2-NH-CH
2CH
2-NH
2), tetraethylenepentamine (TEPA, H
2N-CH
2CH
2-NH-CH
2CH
2-NH-CH
2CH
2-NH-CH
2CH
2-NH
2), pentaethylenehexamine (PEHA, H
2N-CH
2CH
2-NH-CH
2CH
2-NH-CH
2CH
2-NH-CH
2CH
2-NH-CH
2CH
2-NH
2).
*
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:
1,4,7-triazacyclononane ((NHCH
2CH
2)
3) and
cyclen
Cyclen (1,4,7,10-tetraazacyclododecane) is a aza-crown ether with the formula (CH2CH2NH)4. It is a white solid.
Synthesis
Some syntheses exploit the Thorpe-Ingold effect to facilitate ring-formation. Illustrative is the reaction of the depro ...
((NHCH
2CH
2)
4). 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 transitio ...
.
*
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. Abbrev ...
(N(CH
2CH
2NH
2)
3) is a branched polyamine. 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 tridenta ...
.
*
Polyethylenimine
Polyethylenimine (PEI) or polyaziridine is a polymer with repeating units composed of the amine group and two carbon aliphatic ''CHCH'' spacers. Linear polyethyleneimines contain all secondary amines, in contrast to branched PEIs which contain pr ...
is a
polymer
A polymer (; Greek '' poly-'', "many" + ''-mer'', "part")
is a substance or material consisting of very large molecules called macromolecules, composed of many repeating subunits. Due to their broad spectrum of properties, both synthetic a ...
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 derivati ...
.
*Polyethylene polyamine
File:Tris(2-aminoethyl)amine.svg, 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. Abbrev ...
File:Cyclen.svg, Cyclen
Cyclen (1,4,7,10-tetraazacyclododecane) is a aza-crown ether with the formula (CH2CH2NH)4. It is a white solid.
Synthesis
Some syntheses exploit the Thorpe-Ingold effect to facilitate ring-formation. Illustrative is the reaction of the depro ...
File:1,4,7-triazacyclononane.svg, 1,4,7-Triazacyclononane
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 tridenta ...
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 ''CHCH'' spacers. Linear polyethyleneimines contain all secondary amines, in contrast to branched PEIs which contain pr ...
A rare example of a polyamine with only methylene bridges between the nitrogens is
1,3,5-triazinane.
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, 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 growth refers to an increase in the total mass of a cell, including both cytoplasmic, nuclear and organelle volume. Cell growth occurs when the overall rate of cellular biosynthesis (production of biomolecules or anabolism) is greater than ...
. 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 (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment ( ...
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 the flow of io ...
s, including
NMDA receptor
The ''N''-methyl-D-aspartate receptor (also known as the NMDA receptor or NMDAR), is a glutamate receptor and ion channel found in neurons. The NMDA receptor is one of three types of ionotropic glutamate receptors, the other two being AMPA rece ...
s and
AMPA receptor
The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (also known as AMPA receptor, AMPAR, or quisqualate receptor) is an ionotropic receptor, ionotropic transmembrane receptor for glutamate (iGluR) that mediates fast synapse, synap ...
s. They block
inward-rectifier potassium channel
Inward-rectifier potassium channels (Kir, IRK) are a specific lipid-gated subset of potassium channels. To date, seven subfamilies have been identified in various mammalian cell types, plants, and bacteria. They are activated by phosphatidylinos ...
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 prevents solutes in the circulating blood from ''non-selectively'' crossing into the extracellular fluid of ...
.
They are involved in modulating
senescence
Senescence () or biological aging is the gradual deterioration of functional characteristics in living organisms. The word ''senescence'' can refer to either cellular senescence or to senescence of the whole organism. Organismal senescence inv ...
of organs in plants and are therefore considered as a
plant hormone
Plant hormone (or phytohormones) are signal molecules, produced within plants, that occur in extremely low concentrations. Plant hormones control all aspects of plant growth and development, from embryogenesis, the regulation of organ size, pa ...
. 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 cellular organisms but may ...
(HR)-mediated
double-strand break (DSB) repair.
[Lee CY, Su GC, Huang WY, Ko MY, Yeh HY, Chang GD, Lin SJ, Chi P. Promotion of homology-directed DNA repair by polyamines. Nat Commun. 2019 Jan 8;10(1):65. doi: 10.1038/s41467-018-08011-1. PMID: 30622262; PMCID: PMC6325121] Polyamines enhance the DNA strand exchange activity of
RAD51 recombinase. Depletion of polyamines sensitizes cells to
genotoxic substances such as
ionizing radiation
Ionizing radiation (or ionising radiation), including nuclear radiation, consists of subatomic particles or electromagnetic waves that have sufficient energy to ionize atoms or molecules by detaching electrons from them. Some particles can travel ...
and
ultraviolet
Ultraviolet (UV) is a form of electromagnetic radiation with wavelength from 10 nanometer, nm (with a corresponding frequency around 30 Hertz, PHz) to 400 nm (750 Hertz, THz), shorter than that of visible light, but longer than ...
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. It was originally isolated from semen.
Function
Spermidine is an aliphatic polyamine. Spermidine synthase (SP ...
is synthesized from putrescine, using an aminopropyl group from decarboxylated ''S''-adenosyl-L-methionine (SAM). 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-a ...
.
Spermine
Spermine is a polyamine involved in cellular metabolism that is found in all Eukaryote, eukaryotic cells. The precursor for synthesis of spermine is the amino acid ornithine. It is an essential growth factor in some Bacterium, bacteria as well. ...
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 \rightlefthar ...
.
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 (NH2-(CH2)3-NH-(CH2)3-NH-(CH2)4-NH2) is a structural isomer
In chemistry, isomers are molecules or polyatomic ions with identical molecular formulae – that is, same number of atoms of each element – but distinct arrangements of atoms in space. Isomerism is existence or possibility of isomers.
Iso ...
of spermine and a novel type of 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. 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 protein that is often mutated in human cancers. The p53 proteins (originally thought to be, and often s ...
in a cell leading to restriction of proliferation and apoptosis. 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
{{Plant_hormones
Plant hormones