Polyamines putrescine

Eflornithine (difluoromethylornithine, DFMO) inhibits the ornithine decarboxylase of the polyamine pathway, in both the trypanosome and the mammalian cell, by acting as an irreversible competitor of the natural substrate ornithine. Inhibition of ornithine decarboxylase results in depletion of the polyamines, putrescine, spermidine and spermine, which are essential for cell proliferation. Eflornithine selectively harms the parasite and not the mammalian cells, despite acting as an ornithine decarboxylase inhibitor in both cell types. This selectivity is explained by the lower rate of ornithine decarboxylase production in the parasite, as compared to mammalian cells. Due to the high turnover rate, mammalian cells are capable of quickly replenishing inhibited ornithine decarboxylase by newly... 

The polyamines putrescine, cadaverine, spermidine, and spermine, which are seen at elevated levels in some victims of cancer, were separated on a Technicon (The Technicon Company Chauncey, NY) TSM Amino Acid Analyzer packed with an 8% divinylbenzene-co-polystyrene sulfonated resin with post-column ninhydrin detection.111 Amines such as ethanolamine, noradrenaline, hexamethylene diamine, methoxytryptamine, spermine, and spermidine were separated from amino acids on a DC-4A cation exchange resin.112 A similar approach, using a Beckman Model 121M amino acid analyzer equipped with an AA-20 column, was also successful.113 A Polyamin-pak strong cation exchange column (JASCO) was eluted with a citrate buffer for the detection of putrescene, spermine, cadaverine, and 1,5-diaminohex-ane from rat thymus.114 A post-column o-phthaldehyde detection system was used. 

The aliphatic polyamines, putrescine, spermine, and spermidine, are present in green coffee beans, but they are all decomposed during the roasting process.17... 

Experiments utilizing D,L-a-difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decatboxylase, to determine its effect on mitogen- or al-loantigen-induced lymphocyte proliferation and CTL induction have certain similarities to the inhibition seen in N=0-induced inhibition of lymphocyte function. Stimulation of both mouse and human T cells in the presence of DFMO results in partial inhibition of proliferation which can be reversed by addition of the polyamines putrescine, spermidine, and spermine (Bowlin et al., 1987 McCarthy et al., 1990). lL-2 levels in these lymphocyte cultute supernatants as well... 

The polyamines putrescine, spermidine, and spermine have been identified in Jerusalem artichoke tubers (Serafini-Fracassini et al., 1980), though Phillips et al. (1987) found spermidine, diaminopropane, and cadaverine during the initial 24-h activation and onset of mitosis. Both research groups found a correlation between polyamine levels and early cell division, and that polyamines could induce a limited pattern of cell division. 

A possible involvement of polyamines in the response has been suggested. Prolactin stimulated ornithine decarboxylase activity in Nb2 cells [109]. A specific inhibitor of this enzyme partially blocked the actions of lactogenic hormones on Nb2 cell proliferation [110], and addition of polyamines (putrescine, spermidine or spermine) restored normal growth. However, polyamines alone had no effect on Nb2 cell proliferation, suggesting that they are not the sole or major factors involved in mediating the actions of prolactin on cell growth. 

Abstract Natural polyamines (putrescine, spermidine, spermine) are aliphatic amines containing 2 or more amino groups, and play an important role in regulating cell growth and differentiation. Depletion of polyamine in cells has been known to inhibit cell proliferation or induce cell death. This review summarizes changes in polyamine levels during cell death induced by the selective properties of various heterocycles. 

Inhibitors of DNA synthesis and cell replication are TGF-jl and HPI (= hepatic proliferation inhibitor). Their function is to block the growth-promoting factors once the nominal size of the liver has been reached. The regeneration course is, however, also linked to a complex network of biochemical processes, including the polyamines (putrescine, spermidine and spermine) as well as the precursors of nucleic acids (orotate, thymidine and uridine). (17, 33, 47-49, 55, 56)... 

Polyamine biosynthesis is associated with regulation of a number of metabolic functions including growth of cells in most of the living organisms. In mammals, ornithine is the precursor of aliphatic polyamines. Putrescine, formed by decarboxylation of the former by ornithine decarboxylase, is the first amine formed in polyamine biosynthesis. Putrescine gives rise to the other two polyamines, spermine and spermidine by successive addition of 3-aminopropyl residues derived from S-adenosyl-L-methionine (SAM) in the presence of different enzymes [44] (Chart 7). 

FIGURE 7.26 The structures of the herbicide paraquat (A) and the polyamines putrescine (B) and spermine (C). From Timbrell, J.A., Introduction to Toxicology, Taylor and Francis, London, 1989. 

Identified in green and roasted beans by Amorim et al. (1977) by fluorometry and densitometry of the dansyl (5-dimethylamino-l-naphthalenesulfonyl) derivative by TLC. Unlike to the other polyamines, putrescine could be detected in the light-roasted coffee (1-3 ppm), but the polyamine content does not... 

Figure 9 Decarboxylation of t-ornithine leads to the polyamine putrescine, the precursor of sperimidine and sperimine in the polyamine biosynthetic pathway.

Figure 3. Line- and space-filling structures of the polyamines putrescine, spermidine and spermine. With a little imagination, it is possible to envisage how the essentially linear paraquat molecule might fit into a transport system that has evolved to convey these chemicals into lung cells.

Figure 2L10 depicts the synthesis of the polyamines putrescine, spermidine, and spermine. Polyamines are polycationic substances that stabilize intracellular conformations of negatively charged nucleic acids. Polyamines bind to phosphates on both strands of a duplex nucleic acid, thereby stabilizing double-stranded DNA or a duplex region of RNA. 

FIGURE 9.11 HPLC-chromatogram of plum leaf extract purified with Dowex 50W-X8 cation exchange resin. Concentration of polyamines putrescine-0.9 nmol, spermidine-1.6 nmol and spermine-0.2 nmol. (Reproduced with permission from Wehr, J. B. J. Chromatogr. A, 709, 241-247, 1995. Copyright 1995, Elsevier Science.)... 

Conca, R., Concetta Bruzzoniti, M., Mentasti, E., Sarzanini, C., and Hajos, P., Ion chromatographic separation of polyamines putrescine, spermidine and spermine. Anal Chim Acta, 439, 107-114, 2001. 

An investigation of the spermine alkaloids present in the roots of several Aphelandra species has indicated that the polyamines putrescine, spermidine, and spermine interconvert, whereas the alkaloid (- -)-aphelandrine (98) content varies considerably during the first year. This is presumed to be due to the need for the diamine precursors to be used to transport cations, especially during bud formation (55). 

Most pyrrolizidine alkaloids are esters of basic alcohols known as necine bases. The most frequently studied pyrrolizidine alkaloids are formed from the polyamines, putrescine and spermidine, and possess one of three common necine bases retronecine, heliotridine, and otonecine. Putrescine is utilized exclusively as a substrate in secondary metabolism, whereas spermidine is a universal cell-growth factor involved in many physiological processes in eukaryotes. Spermidine biosynthesis begins with the decarboxylation of SAM by SAM decarboxylase 165). The aminopropyl group is then transferred from decarboxylated SAM to putrescine by spermidine synthase to form spermidine (Scheme 5). Putrescine can be produced from ornithine by ODC. However, putrescine is derived from the arginine-agmatine pathway in pyrrolizidine alkaloid-producing plants due to the absence of ODC activity 166). 

Among these polyamines, putrescine is biosynthesized from ornithine by decarboxylation with ornithine decarboxylase. Putrescine receives a propyl-amino rmit (C3N unit) from decarboxylated SAM (S-adenosylmethionine) to form spermidine. SAM is derived from methionine. Spermidine synthase catalyzes this biosynthetic process. Spermine is formed from spermidine through the addition of a C3N unit from a decarboxylated SAM unit under the catalysis of spermine synthase [3]. 

Cytokine-induced neutrophil chemoattractant production in lipopolysaccharide-stimulated rat alveolar macrophages is regulated by the polyamine, putrescine (Kamoi et al. 1997). 

Loading tests are not necessary for the diagnosis of amino acid transport disorders. However, pathophysiologically they may help in differentiating between different types of cystinuria by oral application of cystine and dibasic amino acids followed by analysis of plasma amino acids. The polyamines putrescine and cadaverine are produced intestinally, absorbed and excreted into the urine. Loading with dibasic amino acids will result in increased production of these polyamines [9, 10]. 

Biologically active polyamines putrescine, spermidine and spermine, differ from the traditional group of biogenic amines. Spermidine and spermine arise under specific conditions and they also have different biological effects in comparison with the classical biogenic amines, which are mainly histamine, tyramine, 2-phenylethylamine, putrescine, cadaverine, tryptamine and agmatine. 

Still in connection with the structure of ribosomes, Cohen and Lichtenstein (51) made the interesting observation that in E. coli about 15% of the total polyamines (putrescine and spermidine) of the bacterium are found in the ribosome fraction and that these ribosomal polyamines do not exchange with those in the medium. Moreover, it was found that spermidine acted in conjunction with Mg++ in preserving the structural integrity of the particles. 

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