polyamine

putrescine

cadaverine

spermidine

spermine

A polyamine is an organic compound having two or more primary amino groups -NH₂.

This class of compounds includes several synthetic substances that are important feedstocks for the chemical industry, such as ethylene diamine H2N-CH₂-CH₂-NH₂, 1,3-diaminopropane H₂N-(CH₂)₃-NH₂, and hexamethylenediamine H₂N-(CH₂)₆-NH₂. It also includes many substances that play important roles in both eukaryotic and prokaryotic cells, such as putrescine H₂N-(CH₂)₄-NH₂, cadaverine H₂N-(CH₂)₅-NH₂, spermidine H₂N-((CH₂)₄-NH-)₂-H, and spermine H₂N-((CH₂)₄-NH-)₃-H.

As of 2004, there had been no reports of any geminal diamine, a compound with two or more unsubstituted -NH₂ groups on the same carbon atom. However, substituted derivatives are known, such as tetraethylmethylenediamine, (C₂H₅)₂N-CH₂-N(C₂H₅)₂.^[1]

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, Mg⁺⁺ or Ca⁺⁺, which are point charges).

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.^[2]

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. K+ ion gradient across the cell membrane, is conserved.

Synthesis of linear polyamines

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 .

References

1. ^ Stephen A. Lawrence (2004), Amines: synthesis, properties and applications. Cambridge University Press. ISBN 0521782848, 371 pages.
2. ^ Wang, C.; Delcros, J.-G.; Cannon, L.; Konate, F.; Carias, H.; Biggerstaff, J.; Gardner, R.; Phanstiel, O. Defining the molecular requirements for the selective delivery of polyamine-conjugates into cells containing active polyamine transporters. J. Med. Chem. 2003, 46, 5129-5138.

External links

• Polyamines in cell cycle proliferation and cell death

• Ornithine Decarboxylase: Expression and regulation in rat brain and in transgenic mice, 2002, Pekka Kilpelainen, Department of Biochemistry, University of Oulu. Extensive review of literature through 2001 on polyamine structure, properties, metabolism in mammals, and physiological and pathophysiological roles (See article Table of Contents)