scholarly journals Specificity of mammalian spermidine synthase and spermine synthase

1981 ◽  
Vol 197 (2) ◽  
pp. 315-320 ◽  
Author(s):  
A E Pegg ◽  
K Shuttleworth ◽  
H Hibasami
Keyword(s):  
Small Extent ◽  
Spermidine Synthase ◽  
Mouse Fibroblasts ◽  
Spermine Synthase ◽  
Alpha Omega ◽  
Derivatives Of ◽  
Polyamine Derivatives

1. The specificity of rat prostatic spermidine synthase and spermine synthase with respect to the amine acceptor of the propylamine group was studied. 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. 1,3-Diaminopropane was even less active (2% of the rate with putrescine) and no other compound tested (including longer alpha, omega-diamines, spermidine and its homologues and monoacetyl derivatives) was active. 3. Spermine synthase was equally specific. The only compounds tested that showed any activity were 1,8-diamino-octane, sym-homospermidine, sym-norspermidine and N-(3-aminopropyl)-cadaverine, which at 1mM gave rates 2, 17, 3 and 4% of the rate with spermidine respectively. 4. The formation of polyamine derivatives of cadaverine and to a very small extent of 1,3-diaminopropane was confirmed by exposing transformed mouse fibroblasts to these diamines when synthesis of putrescine was prevented by alpha-difluoromethylornithine. Under these conditions the cells accumulated significant amounts of N-(3-aminopropyl)cadaverine and NN'-bis(3-aminopropyl)cadaverine when exposed to cadaverine and small amounts of sym-norspermidine and sym-norspermine when exposed to 1,3-diaminopropane.

scholarly journals Studies of inhibition of rat spermidine synthase and spermine synthase

1980 ◽  
Vol 187 (2) ◽  
pp. 419-428 ◽  
Author(s):  
Hiroshige Hibasami ◽  
Ronald T. Borchardt ◽  
Shiang Yuan Chen ◽  
James K. Coward ◽  
Anthony E. Pegg
Keyword(s):  
Amino Acid ◽  
Ventral Prostate ◽  
Amino Group ◽  
Spermidine Synthase ◽  
Polyamine Synthesis ◽  
Weak Inhibitor ◽  
Spermine Synthase ◽  
Rat Ventral Prostate ◽  
Potential Inhibitors ◽  
Derivatives Of

1. S-Adenosyl-l-methionine, S-adenosyl-l-homocysteine, 5′-methylthioadenosine and a number of analogues having changes in the base, sugar or amino acid portions of the molecule were tested as potential inhibitors of spermidine synthase and spermine synthase from rat ventral prostate. 2. S-Adenosyl-l-methionine was inhibitory to these reactions, as were other nucleosides containing a sulphonium centre. The most active of these were S-adenosyl-l-ethionine, S-adenosyl-4-methylthiobutyric acid, S-adenosyl-d-methionine and S-tubercidinylmethionine, which were all comparable in activity with S-adenosylmethionine itself, producing 70–98% inhibition at 1mm concentrations. Spermine synthase was somewhat more sensitive than spermidine synthase. 3. 5′-Methylthioadenosine, 5′-ethylthioadenosine and 5′-methylthiotubercidin were all powerful inhibitors of both enzymes, giving 50% inhibition of spermine synthase at 10–15μm and 50% inhibition of spermidine synthase at 30–45μm. 4. S-Adenosyl-l-homocysteine was a weak inhibitor of spermine synthase and practically inactive against spermidine synthase. Analogues of S-adenosylhomocysteine lacking either the carboxy or the amino group of the amino acid portion were somewhat more active, as were derivatives in which the ribose ring had been opened by oxidation. The sulphoxide and sulphone derivatives of decarboxylated S-adenosyl-l-homocysteine and the sulphone of S-adenosyl-l-homocysteine were quite potent inhibitors and were particularly active against spermidine synthase (giving 50% inhibition at 380, 50 and 20μm respectively). 5. These results are discussed in terms of the possible regulation of polyamine synthesis by endogenous nucleosides and the possible value of some of the inhibitory substances in experimental manipulations of polyamine concentrations. It is suggested that 5′-methylthiotubercidin and the sulphone of S-adenosylhomocysteine or of S-adenosyl-3-thiopropylamine may be particularly valuable in this respect.

Regulation of polyamine content in cultured fibroblasts

1982 ◽  
Vol 243 (5) ◽  
pp. C262-C269 ◽  
Author(s):  
D. R. Bethell ◽  
H. Hibasami ◽  
A. E. Pegg
Keyword(s):  
Growth Period ◽  
Transformed Cells ◽  
Biosynthetic Enzymes ◽  
Spermidine Synthase ◽  
3T3 Cells ◽  
Cultured Fibroblasts ◽  
Mouse Fibroblasts ◽  
Adenosylmethionine Decarboxylase ◽  
Spermine Synthase ◽  
Polyamine Content

The content of putrescine and of the polyamines (spermidine and spermine) and the activities of their biosynthetic enzymes were measured in 3T3 mouse fibroblasts and SV40-transformed mouse fibroblasts over the entire period from subculturing in fresh medium until confluence. The transformed cells had a substantially higher content of putrescine and spermidine than the 3T3 cells and higher activities of all of the biosynthetic enzymes. However, the ratio of spermine synthase to spermidine synthase was higher in the 3T3 cells, which correlated with their higher spermine-to-spermidine ratio. All of the biosynthetic enzymes increased in activity during cell growth. Ornithine decarboxylase increased 20-fold with a maximum at 24-36 h after culturing whereas S-adenosylmethionine decarboxylase increased 3-fold at the same time. Spermidine synthase increased 10- to 16-fold during the growth period whereas spermine synthase increased 2- to 3-fold. The relative enzyme activities and the changes in total polyamine content suggested that 1) the activity of S-adenosylmethionine decarboxylase limited the production of the polyamines and 2) the relative amounts of spermidine and spermine synthase determined the predominant polyamine that the available decarboxylated S-adenosylmethionine is used to synthesize. When 3T3 cells become quiescent at confluence, there was a substantial fall in the intracellular spermidine level because of a greatly increased excretion of spermidine into the medium. Spermine content also fell because there was an increased conversion of spermine into spermidine, which was then excreted. The specific excretion of spermidine did not occur with the transformed SV-3T3 cells.

Fluorescence Enhancement of Polyamine Derivatives of 1,8-Naphthalimide with Transition Metal Ions

2006 ◽  
Vol 19 (6) ◽  
pp. 506-510 ◽  
Author(s):  
Guo-tao Wen ◽  
Man-zhou Zhu ◽  
Zhuo Wang ◽  
Xiang-ming Meng ◽  
Hui-yuan Hu ◽  
...  
Keyword(s):  
Transition Metal ◽  
Metal Ions ◽  
Fluorescence Enhancement ◽  
Transition Metal Ions ◽  
Derivatives Of ◽  
Polyamine Derivatives

scholarly journals Polyamine Homeostasis in Snyder-Robinson Syndrome

2018 ◽  
Vol 6 (4) ◽  
pp. 112 ◽  
Author(s):  
Tracy Murray-Stewart ◽  
Matthew Dunworth ◽  
Jackson Foley ◽  
Charles Schwartz ◽  
Robert Casero
Keyword(s):  
Tissue Transglutaminase ◽  
Decarboxylase Activity ◽  
Loss Of Function ◽  
Transport Activity ◽  
Spermine Synthase ◽  
Catabolic Enzymes ◽  
Polyamine Transport ◽  
Exogenous Spermine ◽  
Mutant Cells ◽  
Derivatives Of

Loss-of-function mutations of the spermine synthase gene (SMS) result in Snyder-Robinson Syndrome (SRS), a recessive X-linked syndrome characterized by intellectual disability, osteoporosis, hypotonia, speech abnormalities, kyphoscoliosis, and seizures. As SMS catalyzes the biosynthesis of the polyamine spermine from its precursor spermidine, SMS deficiency causes a lack of spermine with an accumulation of spermidine. As polyamines, spermine, and spermidine play essential cellular roles that require tight homeostatic control to ensure normal cell growth, differentiation, and survival. Using patient-derived lymphoblast cell lines, we sought to comprehensively investigate the effects of SMS deficiency on polyamine homeostatic mechanisms including polyamine biosynthetic and catabolic enzymes, derivatives of the natural polyamines, and polyamine transport activity. In addition to decreased spermine and increased spermidine in SRS cells, ornithine decarboxylase activity and its product putrescine were significantly decreased. Treatment of SRS cells with exogenous spermine revealed that polyamine transport was active, as the cells accumulated spermine, decreased their spermidine level, and established a spermidine-to-spermine ratio within the range of wildtype cells. SRS cells also demonstrated elevated levels of tissue transglutaminase, a change associated with certain neurodegenerative diseases. These studies form a basis for further investigations into the leading biochemical changes and properties of SMS-mutant cells that potentially represent therapeutic targets for the treatment of Snyder-Robinson Syndrome.

scholarly journals Response of enzymes involved in the metabolism of polyamines to phytohaemagglutinin-induced activation of human lymphocytes

1981 ◽  
Vol 196 (3) ◽  
pp. 733-738 ◽  
Author(s):  
H Korpela ◽  
E Hölttä ◽  
T Hovi ◽  
J Jänne
Keyword(s):  
Ornithine Decarboxylase ◽  
Human Lymphocytes ◽  
Lymphocyte Activation ◽  
Decarboxylase Activity ◽  
Spermidine Synthase ◽  
Irreversible Inhibitor ◽  
Adenosylmethionine Decarboxylase ◽  
Spermine Synthase ◽  
Diamine Oxidase Activity ◽  
Stimulation Of

The stimulation of lymphocyte ornithine decarboxylase and adenosylmethionine decarboxylase produced by phytohaemagglutinin was accompanied by an equally marked, but delayed, stimulation of spermidine synthase, which is not commonly considered as an inducible enzyme. In contrast with the marked stimulation of these biosynthetic enzymes, less marked changes were observed in the biodegradative enzymes of polyamines in response to phytohaemagglutinin. Diamine oxidase activity was undetectable during all stages of the transformation. The activity of polyamine oxidase remained either constant or was slightly decreased several days after addition of the mitogen. The activity of polyamine acetylase (employing all the natural polyamines as substrates) distinctly increased both in the cytosolic and crude nuclear preparations of the cells during later stages of mitogen activation. Difluoromethylornithine, an irreversible inhibitor of ornithine decarboxylase, although powerfully inhibiting ornithine decarboxylase, produced a gradual enhancement of adenosylmethionine decarboxylase activity during lymphocyte activation, without influencing the activities of the two propylamine transferases (spermidine synthase and spermine synthase).

Effects of inhibitors of spermidine synthase and spermine synthase on polyamine synthesis in rat tissues

1993 ◽  
Vol 45 (9) ◽  
pp. 1897-1903 ◽  
Author(s):  
Akira Shirahata ◽  
Norio Takahashi ◽  
Takanobu Beppu ◽  
Harumi Hosoda ◽  
Keijiro Samejima
Keyword(s):  
Rat Tissues ◽  
Spermidine Synthase ◽  
Polyamine Synthesis ◽  
Spermine Synthase
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