Apolyamine is anorganic compound having two or moreamino groups. Alkyl polyamines occur naturally, but some are synthetic. Alkylpolyamines are colorless,hygroscopic, and water soluble. Near neutral pH, they exist as the ammonium derivatives.[1][2] Mostaromatic polyamines are crystalline solids at room temperature.
Low-molecular-weight linear polyamines are found in all forms of life. The principal examples are the triaminespermidine and the tetraaminespermine. They are structurally and biosynthetically related to the diaminesputrescine andcadaverine. Polyamine metabolism is regulated by the activity of the enzymeornithine decarboxylase (ODC).[3] Polyamines are found in high concentrations in themammalianbrain.[4]
Ethyleneamines are a commercially-important class of synthetic polyamines with ethylene (−CH2CH2− linkages); global production capacity was estimated at 385,000 tonnes in 2001.[5] They are chemical intermediates often used to make surfactants and as crosslinkers ("hardeners") forepoxy resins.[6] Some members of this class include:
Other synthetic polyamines include1,3,5-triazinane (not to be confused with1,3,5-triazine) and N-substituted analogs. The methylene (−CH2) linkages are derived fromformaldehyde. The reaction product of monoethanolamine and formaldehyde is known industrially as "MEA triazine" (it is actually a triazinane), and it serves as a water-solublehydrogen sulfide scavenger.[8]Hexamethylenetetramine (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 withalkyl halides to selectively prepare primary amines in theDelépine reaction.
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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 toDNA, and, in structure, they represent compounds with cations that are found atregularly spaced intervals (in contrast toMg2+
orCa2+
, which are point charges). They have also been found to act as promoters of programmed ribosomal frameshifting during translation.[9]
Inhibition of polyamine biosynthesis retards or stopscell growth. The provision of exogenous polyamines restores the growth of these cells. Most eukaryotic cells express apolyamine-transporting ATPase on theircell 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.[10]
Polyamines are also modulators of a variety ofion channels, includingNMDA receptors andAMPA receptors. They blockinward-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. 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-producingE. coli under stress conditions.[11]
Polyamines can enhance the permeability of theblood–brain barrier.[12]
They are involved in modulatingsenescence of organs in plants and are therefore considered as aplant hormone.[13] In addition, they are directly involved in regulation ofprogrammed cell death.[14]
Polyamines promotehomologous recombination (HR)-mediateddouble-strand break (DSB) repair.[15] Polyamines enhance the DNA strand exchange activity ofRAD51recombinase. Depletion of polyamines sensitizes cells togenotoxic substances such asionizing radiation andultraviolet 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.[15] Polyamines appear to have an evolutionarily conserved role in regulating recombinase activity.
Spermidine is synthesized from putrescine, using an aminopropyl group from decarboxylatedS-adenosyl-L-methionine (SAM),S-Adenosylmethioninamine. The reaction is catalyzed byspermidine synthase.[16]
Spermine is synthesized from the reaction of spermidine with SAM in the presence of the enzymespermine synthase.
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.[16]
Thermospermine (NH2−(CH2)3−NH−(CH2)3−NH−(CH2)4−NH2) is a structuralisomer of spermine and a plant growth regulator. It is produced from spermidine by the action ofthermospermine synthase, which is encoded by a gene named ACAULIS5 (ACL5).[17]
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 incancer therapy. Polyamine analogues upregulatep53 in a cell leading to restriction of proliferation andapoptosis.[18] It also decreases the expression of estrogen receptor alpha in ER-positive breast cancer.[19]
