Spermine synthesis

Figure 31-3. Arginine, ornithine, and proline metabolism. Reactions with solid arrows all occur in mammalian tissues. Putrescine and spermine synthesis occurs in both mammals and bacteria. Arginine phosphate of invertebrate muscle functions as a phosphagen analogous to creatine phosphate of mammalian muscle (see Figure 31-6).

The enzymatic decarboxylation of AdoMet to produce thej -methyladenosyl-homocysteamine (decarboxylated AdoMet) that is required for Eqs. (13) and (14) has been demonstrated in extracts of a number of plants (Coppoc et al., 1971 Baxter and Coscia, 1973 Suresh and Adiga, 1977). Enzymatic synthesis of spermidine from putrescine and 5-methyladenosylhomocyste-amine [Eq. (13)] has been demonstrated in crude extracts of Vinca rosea seedlings (Baxter and Coscia, 1973). Spermine synthesis appears not to have been studied in plants, but is assumed to proceed by Eq. (14), catalyzed by spermine synthase, as has been established in mammals (Hannonen et al., 1972). 

Recent data reported by Raina on the inhibition of MTA on spermine synthase from bovine brain are particularly interesting in that indicate that the nucleoside may play a role in the regulation of spermine synthesis in animal tissues. They also suggest that the thioether or its nucleosidase resistant derivatives, e.g. me-thylthiotubercidin and dimethylthioadenosine (see Fig. 8), could exert their effect also in vivo, therefore acting as possible antiproliferative agents. 

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-... 

Guminski Y, Grousseaud M, Cugnasse S et al (2009) Synthesis of conjugated spermine derivatives with 7-nitrobenzoxadiazole (NBD), rhodamine and bodipy as new fluorescent probes for the polyamine transport system. Bioorg Med Chem Lett 19 2474—2477... 

Figure 11.9 Schematic view of the experimental strategy for carrying out poly(Phe) synthesis in POPC liposomes, (i) Freeze-thaw (x 7) solution containing t-RNAP , poly(U), Phe, ATP, GTP, Mg(OAc)2, NH4CI, spermine, spermidine, phos-phoenolpyruvate. (ii) Soution containing pyruvate kinase, 100 000 g supernatant enzymes, 308 and SOS ribosomal subunits, (iii) 1. Free-thaw (x3) 2. Brief extrusion 3. Addition of EDTA (final concentration = 35 mM. (iv) Withdrawl of aliquots at indicated time and cold TCA precipitation. Analysis of the radioactivity remaining on the glass filter by p-scintillation counting. (Modified from Oberholzer et al, 1999.)...

Fillingame, R. H., Jorstad, C. M., and Morris, D. R. (1975). Increased cellular levels of spermidine or spermine are required for optimal DNA synthesis in lymphocytes activated by concanavalin A. Proc. Natl. Acad. Sci. U.S.A. 72, 4042-4045. 

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. 

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). 

A systematic analysis to determine the biophysical characteristics of some cationic lipid/DNA complexes from this series was undertaken (Eastman et al., 1997). Product 1 (Figure 15.7) is currently being used in clinical trials as a carrier of CFTR gene in cystic fibrosis. The synthesis of these cholesteryl derivatives is similar to that of DC-Chol cholesteryl chloroformate is reacted with spermine or spermidine as polycation (Lee et al., 1996). 

Soltan MK, Ghonaim HM, El Sadek M et al (2009) Design and synthesis of N-4, N-9-disubstituted spermines for non-viral siRNA delivery - structure-activity relationship studies of transfection efficiency versus toxicity. Pharm Res 26 286-295... 

Fig. 1 (a) Synthesis of dextran-spermine conjugates, (b) Fluorescence micrographs of dextran-spermine compared to common transfection reagents in HEK293 and NIH3T3 cells. Adapted with permission from [38]. 2002 American Chemical Society... 

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