Putrescine spermidine synthesis

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. 

Figure 21.10 depicts synthesis of putrescine, spermidine, and spermine from ornithine. Putrescine is synthesized by decarboxylation of ornithine and it derives its name from the fact it was originally isolated from rotting meat. Putrescine is a precursor to spermidine, then to spermine through the AdoMet-mediated transfer of active propylamino groups... 

Figure 21.10 depicts synthesis of putrescine, spermidine, and spermine from ornithine.The "H3N ... 

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-... 

Figure 9.2. Metabolism of pyrrolizidine alkaloids (PAs) in Senecio vernalis. The substrates for alkaloid biosynthesis, putrescine and spermidine, are derived from primary metabolism. Homospermidine, synthesized by homospermidine synthase (HSS), is the first pathway specific intermediate. It is exclusively incorporated into the necine base moiety of senecionine A-oxide, the backbone structure of all PAs found in this Senecio species. During allocation from the roots as site of synthesis to the shoots, it is chemically modified to provide the species specific PA-pattem.

Cells treated with 5-FU undergo cell cycle arrest or apoptosis by inhibition of DNA synthesis. When human oral squamous cell carcinomas (HSC-2, HSC-3, HSC-4) were treated with 5-FU, viable cell numbers declined dose-dependently (CC50 determined after 24 hours treatment 3.4,6.9 and 1.7 p,M, respectively). The intracellular putrescine concentration slightly declined (Table 2) [29]. The combination treatment of 5-FU with N(l),N(ll)-diethylnorspermine (DEN-SPM), which is an inducer of spermidine/spermine N(l)-acetyltransferase (SSAT) that depletes polyamine, has been reported to augment the cytotoxic activity of 5-FU, suggesting possible clinical application [30]. 

Putrescine Is the precursor for synthesis of spermine and spermidine by reaction with decarboxylated S-adenosyl-methlonlne. 

Like helminths, some protozoans also require polyamines for their cell growth, membrane stabilization and as cofactors for macromolecular synthesis. Trypanosomes have been found to possess putrescine and spermidine, but not spermine. The precursor of the polyamine biosynthesis in protozoans is ornithine, which is de-carboxylated in the presence of ornithine decarboxylase to form putrescine. Other polyamines are formed from putrescine as discussed in chapter 2 (Sec. 5.3). 

Metcalf et al. (23) reported the synthesis of efiornithine (difluoromethyl ornithine [DFMO]) in 1978. Their interest arose from the desire to prepare ornithine decarboxylase (ODC) inhibitors as tools for studying the role of polyamines as regulators of growth processes. Ornithine decarboxylase catalyzes the conversion of ornithine to putrescine (1,4-diaminobutane), which in turn leads to the formation of the polyamines, spermine, and spermidine. It was not until 1980 that Bacchi et al. (24) demonstrated the potential of DFMO in the treatment of trypanosomiasis. 

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). 

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