Spermidine and spermine

Similar to the sitnation with DNA structures formed under osmotic stress, DNA strands in cation-condensed bundles were found to be hexagonally packed and to possess liqnid crystalline order. For example, spermine and spermidine-condensed samples were fonnd to contain a cholesteric phase [70]. Surprisingly, DNA condensed with (Co(NH3)6) failed to exhibit a liquid crystalline ordering [47]. 

Adenosylmethionine, the principal source of methyl groups in the body, also contributes its carbon skeleton for the biosynthesis of the 3-diaminopropane portions of the polyamines spermine and spermidine (Figure 31-4). 

Arginine is the formamidine donor for creatine synthesis (Figure 31-6) and via ornithine to putrescine, spermine, and spermidine (Figure 31-3) Arginine is also the precursor of the intercellular signaling molecule ni-... 

Adenosylmethionine, the methyl group donor for many biosynthetic processes, also participates direcdy in spermine and spermidine biosynthesis. 

S-adenosylmethionine carboxylase is the source of the propylamine in the polyamines spermine and spermidine. The activity of spermine synthase introduces this into spermidine and spermine, which has already been noted. It is worth pointing out that, whereas the inducible histidine decarboxylase... 

Figure 9 summarizes the electrode responses toward a variety of DNA-binding substrates [14c]. For intercalators (quinacrine, acridine orange, and safranin) and groove binders (spermine and spermidine), a steep rise followed by a saturation of the concentration response curve is commonly observed. If one compares the specific concentration which gives a 50% response in the increment of the cathodic peak current (A/p ) for each substrate, a selectivity order of quinacrine acridine orange > spermine > spermidine > safranin can be estimated. The binding constants measured in aqueous media for the affinity reaction with ds DNA are as follows quinacrine, 1.5 x 10 (38 mM NaCl)... 

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... 

In addition to the glutamate and glycine sites on the NMDA receptor, there also exist polyamine sites which are activated by the naturally occurring polyamines spermine and spermidine. Specific divalent cation sites are also associated with the NMDA receptor, namely the voltage-dependent magnesium site and the inhibitory zinc site. In addition to the excitatory amino acids, the natural metabolite of brain tryptophan, quinolinic acid, can also act as an agonist of the NMDA receptor and may contribute to nerve cell death at high concentrations. 

Polyamine oxidase (amine oxygen oxidoreductase, deaminating, flavin-containing), is also a FAD-dependent enzyme and has many similarities to MAO. It is responsible for the oxidation of the secondary amino group in such substrates as A/-acetyl spermine and spermidine in the biosynthesis of spermidine and putrescine [1,12], This enzyme will not be covered in this chapter. 

Polyamines such as spermine and spermidine, involved in DNA packaging, are derived from methionine and ornithine by the pathway shown in Figure 22-30. The first step is decarboxylation of ornithine, a precursor of arginine (Fig. 22-10). Ornithine decarboxylase, a PLP-requiring enzyme, is the target of several powerful inhibitors used as pharmaceutical agents (Box 22-2). ... 

Many studies on the cationic trypanocides have failed to identify their site(s) of action. A recent proposal is that their activity is due to interaction with biologically active polyamines, e.g. spermine and spermidine (80MI10809). These and other polyamines have significant roles in cell division and macromolecular synthesis. 

Fage D., Voltz C., Scatton B., and Carter C. (1992). Selective release of spermine and spermidine from the rat striatum by N-methyl-D-aspartate receptor activation in vivo. J. Neurochem. 58 2170-2175. 

Ornithine decarboxylase catalyzes the transformation of ornithine to the polycationic bases, putresine, spermine, and spermidine. These compounds exert regulatory effects on cell growth. It has been shown that quercetin (10 to 30 pmol/mouse) markedly suppressed the stimulatory effect of the transporters associated with antigen processing (TPA) on ornithine decarboxylase (ODC) activity and on skin tumor formation in mice initiated with dimethylbenzanthracene. Such inhibition may be related to the activation of the catalytic site, which is under nonconventional regulation by small molecules. Also, the synthetic flavonoid flavone acetic acid was shown to inhibit the activity of ODC in stimulated human peripheral blood lymphocytes and human colonic lamina propria lymphocytes. 

This plant, native to New Caledonia, has yielded four new alkaloids which show affinities with spermine and spermidine. 

Figure 14.8. Sites of action of endogenous ligands and drugs that modulate the action of excitatory amino acids on the NMDA receptor. Recent evidence shows that glutamate (Glut) and possibly other excitatory amino acids released from presynaptic terminals activate the NMDA receptor site on postsynaptic membranes, resulting in the opening of the Na+/Ca++ channels. Glycine acts on a strychnine-insensitive receptor while polyamines (e.g. spermine and spermidine) also have a modulatory role. Conversely Zn++ and Mg++ and drugs like phencyclidine (PCP) block the ion channel by acting at various sites on the NMDA receptor complex or...

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