Publications

• Aminopropyltransferases: function, structure and genetics.

  Ikeguchi Y., Bewley M.C., Pegg A.E.

  Aminopropyltransferases use decarboxylated S-adenosylmethionine as an aminopropyl donor and an amine acceptor to form polyamines. This review covers their structure, mechanism of action, inhibition, regulation and function. The best known aminopropyltransferases are spermidine synthase and spermin ... >> More

  Aminopropyltransferases use decarboxylated S-adenosylmethionine as an aminopropyl donor and an amine acceptor to form polyamines. This review covers their structure, mechanism of action, inhibition, regulation and function. The best known aminopropyltransferases are spermidine synthase and spermine synthase but other members of this family including an N(1)-aminopropylagmatine synthase have been characterized. Spermidine synthase is an essential gene in eukaryotes and is very widely distributed. Key regions in the active site, which are very highly conserved, were identified by structural studies with spermidine synthase from Thermotoga maritima bound to S-adenosyl-1,8-diamino-3-thiooctane, a multisubstrate analog inhibitor. A general mechanism for catalysis by aminopropyltransferases can be proposed based on these studies. Spermine synthase is less widely distributed and is not essential for growth in yeast. However, Gy mice lacking spermine synthase have multiple symptoms including a profound growth retardation, sterility, deafness, neurological abnormalities and a propensity to sudden death, which can all be prevented by transgenic expression of spermine synthase. A large reduction in spermine synthase in human males due to a splice site variant causes Snyder-Robinson syndrome with mental retardation, hypotonia and skeletal abnormalities. << Less

  J Biochem 139:1-9(2006) [PubMed] [EuropePMC]

• Kinetic properties of spermine synthase from bovine brain.

  Pajula R.L.

  A kinetic analysis including initial-velocity and product-inhibition studies were performed with spermine synthase purified from bovine brain. The enzyme activity was assayed in the presence of 5'-methylthioadenosine phosphorylase as an auxiliary enzyme to prevent the accumulation of the inhibitor ... >> More

  A kinetic analysis including initial-velocity and product-inhibition studies were performed with spermine synthase purified from bovine brain. The enzyme activity was assayed in the presence of 5'-methylthioadenosine phosphorylase as an auxiliary enzyme to prevent the accumulation of the inhibitory product, 5'-methylthioadenosine, and thus to obtain linearity of the reaction with time. Initial-velocity studies gave intersecting or converging linear double-reciprocal plots. No substrate inhibition by decarboxylated S-adenosylmethionine was observed at concentrations up to 0.4 mM. Apparent Michaelis constants were 60 microM for spermidine and 0.1 microM for decarboxylated S-adenosylmethionine. Spermine was a competitive product inhibitor with respect to decarboxylated S-adenosylmethionine, but a mixed one with respect to the other substrate, spermidine. 5'-Methylthioadenosine showed a mixed inhibition with both substrates, predominantly competitive with respect to decarboxylated S-adenosylmethionine and predominantly uncompetitive with respect to spermidine. The observed kinetic and inhibition patterns are consistent with a compulsory-order mechanism, where both substrates add to the enzyme before products can be released. << Less

  Biochem J 215:669-676(1983) [PubMed] [EuropePMC]

• Spermidine biosynthesis. Purification and properties of propylamine transferase from Escherichia coli.

  Bowman W.H., Tabor C.W., Tabor H.

  J. Biol. Chem. 248:2480-2486(1973) [PubMed] [EuropePMC]

  This publication is cited by 1 other entry.

• Putative spermine synthases from Thalassiosira pseudonana and Arabidopsis thaliana synthesize thermospermine rather than spermine.

  Knott J.M., Romer P., Sumper M.

  Polyamines are involved in many fundamental cellular processes. Common polyamines are putrescine, spermidine and spermine. Spermine is synthesized by transfer of an aminopropyl residue derived from decarboxylated S-adenosylmethionine to spermidine. Thermospermine is an isomer of spermine and assum ... >> More

  Polyamines are involved in many fundamental cellular processes. Common polyamines are putrescine, spermidine and spermine. Spermine is synthesized by transfer of an aminopropyl residue derived from decarboxylated S-adenosylmethionine to spermidine. Thermospermine is an isomer of spermine and assumed to be synthesized by an analogous mechanism. However, none of the recently described spermine synthases was investigated for their possible activity as thermospermine synthases. In this work, putative spermine synthases from the diatom Thalassiosira pseudonana and from Arabidopsis thaliana could be identified as thermospermine synthases. These findings may explain the previous result that two putative spermine synthase genes in Arabidopsis produce completely different phenotypes in knock-out experiments. Likely, part of putative spermine synthases identifiable by sequence comparisons represents in fact thermospermine synthases. << Less

  FEBS Lett. 581:3081-3086(2007) [PubMed] [EuropePMC]

  This publication is cited by 1 other entry.

• Polyamine synthesis in mammalian tissues. Isolation and characterization of spermine synthase from bovine brain.

  Pajula R.L., Raina A., Eloranta T.

  Spermine synthase, a propylamine transferase, which catalyses the biosynthesis of spermine from S-methyladenosylhomocystemine and spermidine has been purified to an apparent homogeneity (about 6000-fold) from bovine brain using spermine-Sepharose affinity chromatography. The enzyme preparation was ... >> More

  Spermine synthase, a propylamine transferase, which catalyses the biosynthesis of spermine from S-methyladenosylhomocystemine and spermidine has been purified to an apparent homogeneity (about 6000-fold) from bovine brain using spermine-Sepharose affinity chromatography. The enzyme preparation was free from S-adenosylmethionine decarboxylase and spermidine synthase activities. The molecular Stokes radius of the enzyme was calculated to be 4.16 nm. The enzyme has an apparent molecular weight of approximately 88 000, composing of two subunits of equal size. The enzyme showed a broad pH optimum between 7.0 and 8.0 and an acidic isoelectric point at pH 5.10. The apparent Km values for S-methyladenosylhomocysteamine was 0.6 microM and about 60 microM for spermidine. The enzyme showed strict specificity to spermidine as the propylamine acceptor. Both the reaction products, spermine and 5'-methylthioadenosine inhibited the enzyme activity, methylthioadenosine being a powerful competitive inhibitor with respect to S-methyladenosylhomocysteamine (Ki value of about 0.3 microM). Putrescine also inhibited competitively with respect to spermidine (Ki value of about 1.7 mM). Spermine synthase had no requirements for metal or other cofactors. << Less

  Eur J Biochem 101:619-626(1979) [PubMed] [EuropePMC]

• Studies of inhibition of rat spermidine synthase and spermine synthase.

  Hibasami H., Borchardt R.T., Chen S.Y., Coward J.K., Pegg A.E.

  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 ... >> More

  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 10-15mum and 50% inhibition of spermidine synthase at 30-45mum. 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 20mum 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. << Less

  Biochem J 187:419-428(1980) [PubMed] [EuropePMC]

• Specificity of mammalian spermidine synthase and spermine synthase.

  Pegg A.E., Shuttleworth K., Hibasami H.

  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 wit ... >> More

  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. << Less

  Biochem J 197:315-320(1981) [PubMed] [EuropePMC]