Nucleic polyamines

A correlation of enhanced synthesis of polyamines with rapid growth or cell proliferation has been observed 21. From a physiological point of view, polyamines are implicated as regulators of cell proliferative activity 22). It is well known that polyamines, as protonated polycations, can bind with nucleotide and nucleic acid anions 23 241 to affect biochemical reactivities and stabilize tertiary structures 25,26). 

A similar situation is found in the structure of putrescine diphosphate " (a model system for amine-nucleic acid interactions) which divides into layers of HjPOJ anions bridged by protonated putrescine (1,4-diamino-n-butane) cations. In a real biological system (yeast phenylalanine transfer RNA) phosphate residues are found to be enveloped by the polyamine spermine [NH2(CH2)jNH(CH2)4NH(CH2)jNH2] which again adopts a linear, nonchelating conformation. ... 

This is a sedative drug with low adult toxicity, which proved to be a very potent human teratogen, causing phocomelia (shortening of the limbs) and other defects when taken between the third and eighth week. In some cases, only a few doses were taken, but on the critical days (e.g., days 24-27 for phocomelia of arms). It is not readily reproducible in laboratory animals (e.g., rats). Mechanism is unknown, but a metabolite suspected, possibly produced by cytochrome P-450. A number of metabolites are produced and some chemical breakdown occurs. Phthalylglutamic acid metabolite is teratogenic in mice. Thalidomide may acylate nucleic acids and polyamines. The S-enantiomer is more embryotoxic than the R-enantiomer. 

Adenine phosphoribosyltransferase catalyzes the conversion of adenine to AMP in many tissues, by a reaction similar to that of hypoxanthine-guanine phosphoribosyltransferase, but is quite distinct from the latter. It plays a minor role in purine salvage since adenine is not a significant product of purine nucleotide catabolism (see below). The function of this enzyme seems to be to scavenge small amounts of adenine that are produced during intestinal digestion of nucleic acids or in the metabolism of 5 -deoxy-5 -methylthioadenosine, a product of polyamine synthesis. 

Polyamines like spermidine and spermine, which bind tightly to nucleic acids and are abundant in rapidly proliferating cells, are present in parasitic helminths in amounts comparable to those in vertebrate cells. As the enzymes necessary for their synthesis are lacking in adult parasitic flatworms, it is assumed that these compounds are obtained from the host (Bacchi and Yarlett, 1 995). In F. hepatica a polyamine N-acetyltransferase has been characterized, that is thought to play a major role in the polyamine metabolism of this parasite by inactivating excess amines (Aisien and Walter, 1993). 

Several authors describe distinct classes of chemical transfection reagents. Fischer et al. summarize synthesis methods, features, and applications of hyper-branched polyamines as carriers for nucleic acids. 

Ion pair interactions are also present in natural supramolecular systems (e.g. DNA-peptides, polyamine-nucleic acids and among proteins or enzymes). Such kinds of attractive forces are strongly dependent on the ionic strength (I) of the solution if extrapolated to I = 0 the average value for the free energy of association for one cation-anion pair is about 8 KJ/mol, and... 

Serafini-Fracassini, D., Bagni, N., Cionini, P.G., and Bennie, A., Polyamines and nucleic acids during the first cells cycle of Helianthus tuberosus tissue after the dormancy break, Planta, 148, 332-337, 1980. 

Serafini-Fracassini, D., Torrigiani, P., and Branca, C., Polyamines bound to nucleic acids during dormancy and activation of tuber cells of Helianthus tuberosus, Plant Physiol., 60, 351-357, 1984. 

Amino acid side chains, nucleic acids (low pH) Biological polyamines Amino acids, biological polyamines Ammonium ion... 

Tung CH, Breslauer KJ, Stein S (1993) Polyamine-linked oligonucleotides for DNA triplehelix formation. Nucleic Acids Res 21 5489-5494... 

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)... 

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. 

Polyamine biosynthesis is closely related to the proliferative state of the cell. When nucleic acid synthesis is activated, so is polyamine synthesis. 

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