Polyamine

From Wikipedia, the free encyclopedia
Jump to: navigation, search

A polyamine is an organic compound having two or more primary amino groups –NH
2
.

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

As of 2004, there had been no reports of any geminal diamine, a compound with two or more unsubstituted –NH
2
groups on the same carbon atom. However, substituted derivatives are known, such as tetraethylmethylenediamine, (C
2
H
5
)
2
N–CH
2
–N(C
2
H
5
)
2
.[1]

Piperazine is an example of a cyclic polyamine. Cyclen and cyclam are examples of macrocyclic polyamines. Polyethylene amine is a polymer based on aziridine monomer.

Functions[edit]

Biological[edit]

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, Mg2+
or Ca2+
, which are point charges). They have also been found to act as promoters of programmed ribosomal frameshifting during translation.[2]

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.[3]

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 cellul 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-producing E. coli under stress conditions.[4]

Polyamines can enhance the permeability of the blood–brain barrier.[5]

They are involved in modulating senescence of organs in plants and are therefore considered as a plant hormone.[6] In addition, they are directly involved in regulation of programmed cell death [7]

Chelating agents[edit]

Ethylenediamine ligand, binding to a central atom with two bonds

Polyamines are important chelating agents. tetramethylethylenediamine (TMED) is useful for dissolving metal ions in organic solvents. Polyamines like eiethylenetriamine(dien) and triethylenetetramine (TETA or trien) and more powerful chelating agents forming tridentate and tetradentate complexes, respectively. Macrocyclic polyamines like cyclam add cavity selectivity to the chelate effect. The heme group in Hemoglobin is an important example of a macrocyclic ligand containing the polyamine motif.

There are aromatic analogues of the aliphatic linear polyamines such as dipyridine, o-phenanthroline and terpyridine which are also useful chelating agents.

Prontonated polyamines, particularly macrocyclic ones, can bind anions. By varying the shape and size of the cavity the protonated polyamine can be engineered to be a specific anion receptor.

Synthesis of linear polyamines[edit]

Putrescine[edit]

Putrescine is synthesized biologically via two different pathways, both starting from arginine.

Cadaverine[edit]

Cadaverine synthesis.svg


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

Spermidine and spermine[edit]

SPD SPM synthesis English.svg

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[edit]

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.[9] It also decreases the expression of estrogen receptor alpha in ER positive breast cancer.[10]

References[edit]

  1. ^ Lawrence, Stephen A. (2004). Amines: synthesis, properties and applications. Cambridge University Press. p. 64. ISBN 978-0-521-78284-5. 
  2. ^ Rato C, Amirova S.R, Bates D.G, Stansfield I, Wallace H.M (June 2011). "Translational recoding as a feedback controller: systems approaches reveal polyamine-specific effects on the antizyme ribosomal frameshift". Nucleic Acid Res. 39 (11): 4587–4597. doi:10.1093/nar/gkq1349. PMC 3113565. PMID 21303766. 
  3. ^ Wang C, Delcros JG, Cannon L et al. (November 2003). "Defining the molecular requirements for the selective delivery of polyamine conjugates into cells containing active polyamine transporters". J. Med. Chem. 46 (24): 5129–38. doi:10.1021/jm030223a. PMID 14613316. 
  4. ^ Yi-Hsuan Pan, Chen-Chung Liao (May 2006). "The critical roles of polyamines regulating ColE7 production and restricting ColE7 uptake of the colicin-producing Escherichia coli". JBC 281 (19): 13083–13091. doi:10.1074/jbc.M511365200. PMID 16549429. 
  5. ^ Zhang L, Lee HK, Pruess TH, White HS, Bulaj G (March 2009). "Synthesis and applications of polyamine amino acid residues: improving the bioactivity of an analgesic neuropeptide, neurotensin". J. Med. Chem. 52 (6): 1514–7. doi:10.1021/jm801481y. PMC 2694617. PMID 19236044. 
  6. ^ Pandey S, Ranade SA, Nagar PK, Kumar N (September 2000). "Role of polyamines and ethylene as modulators of plant senescence". J. Biosci. 25 (3): 291–9. doi:10.1007/BF02703938. PMID 11022232. 
  7. ^ Moschou, PN; Roubelakis-Angelakis, KA (Nov 11, 2013). "Polyamines and programmed cell death.". Journal of Experimental Botany. doi:10.1093/jxb/ert373. PMID 24218329. 
  8. ^ Srivenugopal KS, Adiga PR (September 1981). "Enzymic conversion of agmatine to putrescine in Lathyrus sativus seedlings. Purification and properties of a multifunctional enzyme (putrescine synthase)." 256 (18). pp. 9532–41. PMID 6895223. 
  9. ^ "Role of p53/p21(Waf1/Cip1) in the regulation of polyamine analogue-induced growth inhibition and cell death in human breast cancer cells". Retrieved 21 November 2012. 
  10. ^ "Polyamine analogues down-regulate estrogen receptor alpha expression in human breast cancer cells". Retrieved 21 November 2012. 

External links[edit]