Polyamine

A polyamine is an organic compound having two or more primary amino groups.

This class of compounds includes several synthetic substances that are important feedstocks for the chemical industry, such as ethylene diamine, 1,3-diaminopropane , and hexamethylenediamine. It also includes many substances that play important roles in both eukaryotic and prokaryotic cells, such as putrescine, cadaverine , spermidine , and spermine.

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 is the main representative of a class of cyclic polyamines. Polyethylene amine is a polymer based on aziridine monomer.

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 DNA, and, in structure, they represent compounds with cations that are found at regularly spaced intervals (unlike, say,  or, which are point charges). They have also been found to act as promoters of programmed ribosomal frameshifting during translation.

If cellular polyamine synthesis is inhibited, cell growth 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 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 channels, including NMDA receptors and AMPA receptors. 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. Polyamine may participate in initiating the expression of SOS response of ColE7 operon and down-regulate proteins that are essential for colicin uptake, thus conferring a survival adventage on colicin-producing E. coli under stress conditions.

Polyamines can enhance the permeability of the blood–brain barrier.

They are involved in modulating senescence of organs in plants and are therefore considered as a plant hormone.

Putrescine
Putrescine is synthesized biologically via two different pathways, both starting from arginine.
 * In one pathway, arginine is converted into agmatine, with a reaction catalyzed by the enzyme arginine decarboxylase (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 ornithine and then ornithine is converted into putrescine by ornithine decarboxylase (ODC).

Cadaverine


Cadaverine is synthesized from lysine in a one-step reaction with lysine decarboxylase (LDC).

Spermidine and spermine
Spermidine is synthesized from putrescine, using an aminopropylic group from decarboxylated S-adenosyl-L-methionine (SAM). The reaction is catalyzed by spermidine synthase.

Spermine is synthesized from the reaction of spermidine with SAM in the presence of the enzyme spermine synthase.

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 in a cell leading to restriction of proliferation and apoptosis. It also decreases the expression of estrogen receptor alpha in ER positive breast cancer