Polyamine
Encyclopedia
Organic compound
An organic compound is any member of a large class of gaseous, liquid, or solid chemical compounds whose molecules contain carbon. For historical reasons discussed below, a few types of carbon-containing compounds such as carbides, carbonates, simple oxides of carbon, and cyanides, as well as the...
having two or more primary amino groups .
This class of compounds includes several synthetic substances that are important feedstocks for the chemical industry
Chemical industry
The chemical industry comprises the companies that produce industrial chemicals. Central to the modern world economy, it converts raw materials into more than 70,000 different products.-Products:...
, such as ethylene diamine
Ethylene diamine
Ethylenediamine is the organic compound with the formula C2H42. This colorless liquid with an ammonia-like odor is a strongly basic amine. The liquid fumes upon contact with humid air...
, 1,3-diaminopropane
1,3-Diaminopropane
1,3-Diaminopropane is a simple amine. The potassium salt is used in the alkyne zipper reaction, first reported by Charles Allen Brown and Ayako Yamashita in 1975....
, and hexamethylenediamine
Hexamethylenediamine
Hexamethylenediamine is the organic compound with the formula H2N6NH2. The molecule is a diamine, consisting of a hexamethylene hydrocarbon chain terminated with amine functional groups. The colorless solid has a strong amine odor, similar to piperidine...
. It also includes many substances that play important roles in both eukaryotic and prokaryotic cells, such as putrescine
Putrescine
Putrescine is a foul-smelling organic chemical compound NH24NH2 that is related to cadaverine; both are produced by the breakdown of amino acids in living and dead organisms and both are toxic in large doses...
, cadaverine
Cadaverine
Cadaverine is a foul-smelling compound produced by protein hydrolysis during putrefaction of animal tissue. Cadaverine is a toxic diamine with the formula NH25NH2, which is similar to putrescine...
, spermidine
Spermidine
Spermidine is a polyamine involved in cellular metabolism. Its known actions include:#Inhibition of neuronal nitric oxide synthase, nNOS#Assisting the in vitro process of transcribing RNA via stimulation of T4 polynucleotide kinase and T7 RNA polymerase activity; it binds to and precipitates DNA...
, and spermine
Spermine
Spermine is a polyamine involved in cellular metabolism found in all eukaryotic cells. 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 physiological pH...
.
As of 2004, there had been no reports of any geminal diamine, a compound with two or more unsubstituted groups on the same carbon atom. However, substituted derivatives are known, such as tetraethylmethylenediamine, .
Cyclen
Cyclen
Cyclen or 1,4,7,10-tetraazacyclododecane is a macrocycle and the aza analogue of the crown ether 12-crown-4. Derivatives of cyclen are larger cyclic polyamines but the repeating unit is always the same. Like crown ethers, cyclen compounds are capable of selectively binding cations...
is the main representative of a class of cyclic polyamines. Polyethylene amine
Polyethylene amine
Polyethylene amine is a polymer of aziridine with the molecular formula n. It is a structural analogue of polyethylene glycol with -NH- in place of oxygen atoms. It is produced by the polymerization of aziridine....
is a polymer
Polymer
A polymer is a large molecule composed of repeating structural units. These subunits are typically connected by covalent chemical bonds...
based on aziridine
Aziridine
Aziridines are organic compounds containing the aziridine functional group, a three-membered heterocycle with one amine group and two methylene groups...
monomer
Monomer
A monomer is an atom or a small molecule that may bind chemically to other monomers to form a polymer; the term "monomeric protein" may also be used to describe one of the proteins making up a multiprotein complex...
.
Functions
Though it is known that polyamines are synthesized in cells via highly regulated pathways, their actual function is not entirely clear. As cations, they bind to DNADNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
, and, in structure, they represent compounds with cations that are found at regularly spaced intervals (unlike, say, or , which are point charges).
If cellular polyamine synthesis is inhibited, cell growth
Cell growth
The term cell growth is used in the contexts of cell development and cell division . When used in the context of cell division, it refers to growth of cell populations, where one cell grows and divides to produce two "daughter cells"...
is stopped or severely retarded. The provision of exogenous polyamines restores the growth of these cells. Most eukaryotic cells have a polyamine transporter system on their cell membrane
Cell membrane
The cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...
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 important modulators of a variety of ion channel
Ion channel
Ion channels are pore-forming proteins that help establish and control the small voltage gradient across the plasma membrane of cells by allowing the flow of ions down their electrochemical gradient. They are present in the membranes that surround all biological cells...
s, including NMDA receptor
NMDA receptor
The NMDA receptor , a glutamate receptor, is the predominant molecular device for controlling synaptic plasticity and memory function....
s and AMPA receptor
AMPA receptor
The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor is a non-NMDA-type ionotropic transmembrane receptor for glutamate that mediates fast synaptic transmission in the central nervous system . Its name is derived from its ability to be activated by the artificial glutamate analog AMPA...
s. They block inward-rectifier potassium channels so that the currents of the channels are inwardly rectified, thereby the cellular energy, i.e. ion gradient across the cell membrane, is conserved.
Polyamines can enhance the permeability of the blood-brain barrier
Blood-brain barrier
The blood–brain barrier is a separation of circulating blood and the brain extracellular fluid in the central nervous system . It occurs along all capillaries and consists of tight junctions around the capillaries that do not exist in normal circulation. Endothelial cells restrict the diffusion...
.
They are involved in modulating senescence
Senescence
Senescence or biological aging is the change in the biology of an organism as it ages after its maturity. Such changes range from those affecting its cells and their function to those affecting the whole organism...
of organs in plants and are therefore considered as a plant hormone
Plant hormone
Plant hormones are chemicals that regulate plant growth, which, in the UK, are termed 'plant growth substances'. Plant hormones are signal molecules produced within the plant, and occur in extremely low concentrations. Hormones regulate cellular processes in targeted cells locally and, when moved...
.
Putrescine
PutrescinePutrescine
Putrescine is a foul-smelling organic chemical compound NH24NH2 that is related to cadaverine; both are produced by the breakdown of amino acids in living and dead organisms and both are toxic in large doses...
is synthesized biologically via two different pathways, both starting from arginine
Arginine
Arginine is an α-amino acid. The L-form is one of the 20 most common natural amino acids. At the level of molecular genetics, in the structure of the messenger ribonucleic acid mRNA, CGU, CGC, CGA, CGG, AGA, and AGG, are the triplets of nucleotide bases or codons that codify for arginine during...
.
- In one pathway, arginine is converted into agmatineAgmatineAgmatine is the decarboxylation product of the amino acid arginine and is an intermediate in polyamine biosynthesis. It is discussed as a putative neurotransmitter. It is synthesized in the brain, stored in synaptic vesicles, accumulated by uptake, released by membrane depolarization, and...
, with a reaction catalyzed by the enzyme arginine decarboxylaseArginine decarboxylaseIn enzymology, an arginine decarboxylase is an enzyme that catalyzes the chemical reactionHence, this enzyme has one substrate, L-arginine, and two products, agmatine and CO2....
(ADC); then agmatine is transformed into carbamilputrescine by agmatine imino hydroxylase (AIH). Finally, carbamilputrescine is converted into putrescine. - In the second pathway, arginine is converted into ornithineOrnithineOrnithine is an amino acid that plays a role in the urea cycle.-Role in urea cycle:L-Ornithine is one of the products of the action of the enzyme arginase on L-arginine, creating urea. Therefore, ornithine is a central part of the urea cycle, which allows for the disposal of excess nitrogen....
and then ornithine is converted into putrescine by ornithine decarboxylaseOrnithine decarboxylaseThe enzyme ornithine decarboxylase catalyzes the decarboxylation of ornithine to form putrescine. This reaction is the committed step in polyamine synthesis. In humans, this protein has 461 amino acids and forms a homodimer....
(ODC).
Cadaverine
CadaverineCadaverine
Cadaverine is a foul-smelling compound produced by protein hydrolysis during putrefaction of animal tissue. Cadaverine is a toxic diamine with the formula NH25NH2, which is similar to putrescine...
is synthesized from lysine
Lysine
Lysine is an α-amino acid with the chemical formula HO2CCH4NH2. It is an essential amino acid, which means that the human body cannot synthesize it. Its codons are AAA and AAG....
in a one-step reaction with lysine decarboxylase
Lysine decarboxylase
Lysine decarboxylase is an enzyme that converts lysine to cadaverine....
(LDC).
Spermidine and spermine
SpermidineSpermidine
Spermidine is a polyamine involved in cellular metabolism. Its known actions include:#Inhibition of neuronal nitric oxide synthase, nNOS#Assisting the in vitro process of transcribing RNA via stimulation of T4 polynucleotide kinase and T7 RNA polymerase activity; it binds to and precipitates DNA...
is synthesized from putrescine, using an aminopropylic group from decarboxylated S-adenosyl-L-methionine (SAM). The reaction is catalyzed by spermidine synthase
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 enzyme has a molecular weight of approximately 73,000 kD and is composed of two subunits of equal size....
.
Spermine
Spermine
Spermine is a polyamine involved in cellular metabolism found in all eukaryotic cells. 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 physiological pH...
is synthesized from the reaction of spermidine with SAM in the presence of the enzyme spermine synthase .