Spermine synthase

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... 

The aminopropylation of spermidine into spermine by spermine synthase (SPM synthase) is favored by a higher basicity (ease of protonation) of the nitrogens N-1 and N-4, but also by a lower basicity of N-8 of the butylamino terminal group (more difficult protonation). This last factor enhances the affinity of the substrate for the enzyme. Fluorospermidines could then appear as potential inhibitors of SPM synthase. Indeed, the presence of fluorine atoms in P of an amino group lowers the basicity of the amine the pK value of N-4 is lowered by 2.70 units for... 

Figure 7.65 inhibition of spermine synthase (SPM synthase) by fiuorospermidines, and reiated pKa vaiues. 

H2. Hannonen, P., Raina, A., and Janne, J., Polyamine synthesis in the regenerating rat liver Stimulation of s-adenosylmethionine decarboxylase, and spermidine and spermine synthases after partial hepatectmny. Biochim. Biophys. Acta 273,... 

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). 

Fig. 20.3 Pathway of methionine metabolism. The numbers represent the following enzymes or sequences (1) methionine adenosyltransferase (2) S-adenosylmethionine-dependent transmethylation reactions (3) glycine methyltransferase (4) S-adenosylhomocysteine hydrolase (5) betaine-homocysteine methyltransferase (6) 5-methyltetrahydrofolate homocysteine methyltransferase (7) serine hydroxymethyltransferase (8) 5,10-methylenetetrahydrofolate reductase (9) S-adenosylmethionine decarboxylase (10) spermidine and spermine synthases (11) methylthio-adenosine phosphorylase (12) conversion of methylthioribose to methionine (13) cystathionine P-synthase (14) cystathionine y-lyase (15) cysteine dioxygenase (16) cysteine suplhinate decarboxylase (17) hypotaurine NAD oxidoreductase (18) cysteine sulphintite a-oxoglutarate aminotransferase (19) sulfine oxidase. MeCbl = methylcobalamin PLP = pyridoxal phosphate...

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]. 

Spermine (19) Isolation of spermine synthase by afiinity chromatography 250... 

Putrescine, which is produced by decarboxylation of ornithine, and also arises from agmatine with catalysis by agmatinase, becomes the starting compound for the biosynthesis of spermidine and spermine. These reactions are catalysed by spermidine synthase and spermine synthase, respectively, involving S-adenosyl-L-methionine (for short AdoMet or SAM), and take place from bacteria to mammals (Figure 10.16). S-Adenosyl-L-methionine amide (dSAM) formed by decarboxylation of SAM provides trimethylene amine residue for this biosynthesis, which yields S-methyl-5 -thioadenosine (MTA). 

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. 

Protein(arginine) N-me-thylation Spermine synthase (bovine brain)... 

Spermine synthase (rat ventral prostate) Protein 0-carboxymethyl-ation... 

Hanfrey CC, Pearson BM, Hazeldine S, Lee J, Gaskin DJ, Woster PM et al (2011) Alternative spermidine biosynthetic route is critical for growth of Campylobacter jejuni and is the dominant polyamine pathway in human gut microbiota. J Biol Chem 286 43301 3312 Hanzawa Y, Takahashi T, Michael AJ, Burtin D, Long D, Pineiro M et al (2000) ACAULIS5, an Arabidopsis gene required for stem elongation, encodes a spermine synthase. EMBO J 19 4248-4256... 

Knott JM, Romer P, Sumper M (2007) Putative spermine synthases from Thalassiosirapseudonana and Arabidopsis thaliana synthesize thermospermine rather than spermine. FEBS Lett 581 3081-3086... 

Spermine synthase SPMS At5g53120 Drought, ABA, heat shock... 

Hanzawa Y, Takahashi T, Michael AJ, Burtin D, Long D, Pineiro M, Coupland G, Komeda Y (2000) ACAULIS5, an Arabidopsis gene required for stem elongation, encodes a spermine synthase. EMBO J 19 4248 256... 

Gonzalez ME, Marco F, Minguet EG, Carrasco-Sorli P, Blazquez MA, CarboneU J, Ruiz OA, Pieckenstain IT. (2011) Perturbation of spermine synthase gene expression and transedpt profiling provide new insights on the role of the tetraamine spermine in Arabidopsis defense Pseudomonas viridiflava. Plant Physiol 156 2266—2277... 

Fig. 24.1 Polyamine and glutathione metaboUc pathway differences in parasite and mammalian ceU enzymes involved in polyamine biosynthesis (purple font inside solid ovcds), catabolic enzymes black font inside dashed ovals), and enzymes involved in glutathione metabolism (red font inside solid ovals). ODC ornithine decarboxylase, AdoMetDC S-adenosylmethionine decarboxylase, SpdSyn spermidine synthase, SpmSyn spermine synthase, SMO spermine oxidase, SSAT spermidine/spermine N acetyltransferase, APAO JV acetyl polyamine oxidase, yGCS...

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