Disease relevance of Srm

• The open reading frame encoded a polypeptide of 302 amino acids, displaying 95% similarity to human and 33% similarity to E. coli spermidine synthase [1].
• 6. Cadaverine appeared to be an especially suitable compound for use as an inhibitor of the synthesis of higher polyamines, at least in Ehrlich ascites cells, since this diamine also acted as a competitive inhibitor for putrescine in the spermidine synthase reaction without being incorporated into the higher polyamines [2].
• Antitumor effect of dicyclohexylammonium sulfate, a potent inhibitor of spermidine synthase against P388 leukemia [3].
• The antitumor effect of dicyclohexylammonium sulfate (DCHA), a potent inhibitor of spermidine synthase, was tested on mice inoculated with Ehrlich ascites carcinoma, Ehrlich solid carcinoma and solid sarcoma-180 [4].

High impact information on Srm

• When these genes were expressed in Escherichia coli, A411 had no spermidine synthase activity but did show putrescine N-methyltransferase activity, which is the first enzyme committed to the nicotine biosynthetic pathway, and A622 did not show isoflavone reductase activity [5].
• The A411 gene encodes a 41-kD protein with considerable homology to mammalian spermidine synthase, whereas the A622 gene encodes a 35-kD protein with high homology to isoflavone reductase [5].
• These data concur with the established molecular actions of the two enzyme inhibitors as blockers of ornithine decarboxylase (difluoromethylornithine) and spermidine synthase (dicyclohexylammonium sulfate) [6].
• In order to identify the cellular origin of spermidine and spermine synthesis in the brain, antibodies were raised against recombinant mouse spermidine synthase [7].
• The view that the accumulation of spermidine and spermine is possibly controlled by S-adenosylmethionine decarboxylase was further supported by the finding that tissue spermidine and spermine contents also remained practically normal in hybrid transgenic mice over-expressing both human ornithine decarboxylase and spermidine synthase genes [8].

Biological context of Srm

• We have generated a transgenic mouse line harbouring the functional (chromosome-1-derived) human spermidine synthase (EC 2.5.1.16) gene in their genome [8].
• Nucleotide sequence of mouse spermidine synthase cDNA [1].
• Primary structure of rat spermidine synthase: an example of refining the cDNA-derived amino acid sequence [9].
• The gene encoding spermidine synthase (spsA) was isolated from Dictyostelium discoideum using the technique of insertional mutagenesis [10].

Anatomical context of Srm

• Hormonal regulation of spermidine synthase during the development of mouse mammary epithelium in vitro [11].
• Development of spsA null cells grown in the absence of spermidine produced fruiting bodies that have abnormally short stalks [10].
• However, the ratio of spermine synthase to spermidine synthase was higher in the 3T3 cells, which correlated with their higher spermine-to-spermidine ratio [12].

Associations of Srm with chemical compounds

• The elevated spermidine synthase activity, however, had virtually no effect on tissue putrescine, spermidine or spermine levels [8].
• The primary structure of rat spermidine synthase having the N-terminal acetylated methionine and 98.7% homology with that of the mouse enzyme is presented using a limited amount of the homogeneous enzyme [9].
• 2. Spermidine synthase could use cadaverine (1,5-diaminopentane) instead of putrescine, but the Km for cadaverine was much greater and the rate with 1mM-cadaverine was only 10% of that with putrescine [13].
• 2. Ascites-tumour cells likewise exhibited high activities of L-ornithine decarboxylase (EC 4.1.1.17), S-adenosyl-L-methionine decarboxylase (EC 4.1.1.50), spermidine synthase (EC 2.5.1.16) and spermine synthase [2].
• The method consisted of incubating cell extracts with 3H-decarboxylated S-adenosylmethionine and sodium cyanoborohydride in the presence of a spermidine synthase inhibitor [14].

Other interactions of Srm

• There was a large rise in putrescine and a fall in spermidine and spermine in the liver and lung except for brain within an 8 hr period in response to MGBC, suggesting that these changes resulted from the stabilization of ODC and inhibitions of AdoMetDC and spermidine synthase [15].

Analytical, diagnostic and therapeutic context of Srm

• The transgenic animals expressed the human gene-derived mRNA, as revealed by reverse-transcriptase/PCR analysis, in all tissues studied and displayed tissue spermidine synthase activity that was 2-6 times that in their syngenic littermates [8].
• Rapid assay of spermidine synthase activity for high-performance liquid chromatography [16].
• Northern blot analysis showed that the spsA mRNA is expressed maximally during the vegetative stage and decreases gradually during the 24 h of development [10].

References