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Polyamines pp 437-445 | Cite as

Spermine Synthase Deficiency Resulting in X-Linked Intellectual Disability (Snyder–Robinson Syndrome)

  • Charles E. SchwartzEmail author
  • Xaiojing Wang
  • Roger E. Stevenson
  • Anthony E. Pegg
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 720)

Abstract

Polyamines, small positively charged molecules, are vital for cell proliferation and differentiation. They are found ubiquitously in eukaryotic cells. Additionally, they interact with a wide range of other molecules and some membrane associated receptors. Polyamines, spermidine and spermine, are synthesized by two aminopropyltransferases, spermidine synthase and spermine synthase. Recently, mutations in the latter enzyme have been shown to be responsible for an X-linked intellectual disability condition known as Snyder–Robinson syndrome. Spermine synthase deficiency is thus far the only known polyamine deficiency syndrome in humans.

Key words

Spermine Spermine synthase X-linked intellectual disability Snyder–Robinson ­syndrome Polyamine deficiency 

References

  1. 1.
    Cohen SS (1998) A guide to the polyamines. Oxford University Press, New YorkGoogle Scholar
  2. 2.
    Pegg AE (2009) Mammalian polyamine metabolism and function. IUBMB Life 61:880–894PubMedCrossRefGoogle Scholar
  3. 3.
    Williams K (1997) Interactions of polyamines with ion channels. Biochem J 325:289–297PubMedGoogle Scholar
  4. 4.
    Nichols CG, Lopatin AN (1998) Inward rectifier potassium channels. Annu Rev Physiol 59:171–191CrossRefGoogle Scholar
  5. 5.
    Gerner EW, Meyskens FL Jr (2004) Polyamines and cancer: old molecules, new understanding. Nat Rev Cancer 4:781–792PubMedCrossRefGoogle Scholar
  6. 6.
    Ikeguchi Y, Bewley M, Pegg AE (2006) Aminopropyltransferases: function, structure and genetics. J Biochem 139:1–9PubMedCrossRefGoogle Scholar
  7. 7.
    Cason AL, Ikeguchi Y, Skinner C, Wood TC, Lubs HA, Martinez F, Simensen RJ, Stevenson RE, Pegg AE, Schwartz CE (2003) X-Linked spermine synthase gene (SMS) defect: the first polyamine deficiency syndrome. Eur J Human Genet 11:937–944CrossRefGoogle Scholar
  8. 8.
    de Alencastro G, McCloskey DE, Kliemann SE, Maranduba CM, Pegg AE, Wang X, Bertola DR, Schwartz CE, Passos-Bueno MR, Sertie AL (2008) New SMS mutation leads to a striking reduction in spermine synthase protein function and a severe form of Snyder-Robinson X-linked recessive mental retardation syndrome. J Med Genet 45:539–543PubMedCrossRefGoogle Scholar
  9. 9.
    Becerra-Solano LE, Butler J, Castañeda-Cisneros G, McCloskey DE, Wang X, Pegg AE, Schwartz CE, Sánchez-Corona J, Garcia-Ortiz JE (2009) A missense mutation, p.V132G, in the X-linked spermine synthase gene (SMS) causes Snyder-Robinson syndrome. Am J Med Genet A 149A:328–335PubMedCrossRefGoogle Scholar
  10. 10.
    Snyder RD, Robinson A (1969) Recessive sex-linked mental retardation in the absence of other recognizable abnormalities. Report of a family. Clin Pediatr (Phila) 8:669–674CrossRefGoogle Scholar
  11. 11.
    Arena JF, Schwartz C, Ouzts L, Stevenson R, Miller M, Garza J, Nance M, Lubs H (1996) X-linked mental retardation with thin habitus, osteoporosis, and kyphoscoliosis: linkage to Xp21.3-p22.12. Am J Med Genet 64:50–58PubMedCrossRefGoogle Scholar
  12. 12.
    Mackintosh CA, Pegg AE (2000) Effect of spermine synthase deficiency on polyamine biosynthesis and content in mice and embryonic fibroblasts and the sensitivity of fibroblasts to 1, 3-bis(2-chloroethyl)-N-nitrosourea. Biochem J 351:439–447PubMedCrossRefGoogle Scholar
  13. 13.
    Wiest L, Pegg AE (1998) Assay of spermidine and spermine synthase. In: Morgan DML (ed) Methods in molecular biology. 79. Polyamine protocols. Humana, Totowa, pp 51–58Google Scholar
  14. 14.
    Kabra PM, Lee HK, Lubich WP, Marton LW (1986) Solid-phase extraction and determination of dansyl derivatives of unconjugated and acetylated polyamines by reversed-phase liquid chromatography; improved separation systems for polyamines in cerebrospinal fluid, urine and tissue. J Chromatogr Biomed Appl 380:19–32CrossRefGoogle Scholar
  15. 15.
    Seiler N, Knödgen B (1985) Determination of polyamines and related compounds by reversed-phase high-perfomance liquid chromatography: improved separation systems. J Chromatogr 339:45–57CrossRefGoogle Scholar
  16. 16.
    Häkkinen MR (2010) Polyamine analysis by LC-MS. In: Pegg AE, Casero RA Jr (eds) Methods in molecular biology 720. Polyamine protocols Chapter 33. Humana, TotowaGoogle Scholar
  17. 17.
    Chen GG, Fiori LM, Mamet OA, Turecki G (2010) High-resolution capillary gas chromatography (GC) in combination with mass spectrometry (MS) for quantification of three major polyamines in post-mortem brain cortex. In: Pegg AE Casero RA Jr (eds) Methods in molecular biology 720. Polyamine protocols Chapter 27. Humana, TotowaGoogle Scholar
  18. 18.
    Tang KC, Pegg AE, Coward JK (1980) Specific and potent inhibition of spermidine synthase by the transition-state analog, S-adenosyl-3-thio-1, 8-diaminooctane. Biochem Biophys Res Commun 96:1371–1377PubMedCrossRefGoogle Scholar
  19. 19.
    Wu H, Min J, Zeng H, McCloskey DE, Ikeguchi Y, Loppnau P, Michael AJ, Pegg AE, Plotnikov AN (2008) Crystal structure of human spermine synthase: implications of substrate binding and catalytic mechanism. J Biol Chem 283:16135–16146PubMedCrossRefGoogle Scholar
  20. 20.
    Tang KC, Mariuzza R, Coward JK (1981) Synthesis and evaluation of some stable multisubstrate adducts as specific inhibitors of spermidine synthase. J Med Chem 24:1277–1284PubMedCrossRefGoogle Scholar
  21. 21.
    Shirahata A, Morohoshi T, Samejima K (1988) Trans-4-methylcyclohexylamine, a potent new inhibitor of spermidine synthase. Chem Pharm Bull 36:3220–3222PubMedCrossRefGoogle Scholar
  22. 22.
    Shirahata A, Morohohi T, Fukai M, Akatsu F, Samejima K (1991) Putrescine or spermidine binding site of aminopropyltransferases and competitive inhibitors. Biochem Pharmacol 41:205–212PubMedCrossRefGoogle Scholar
  23. 23.
    Pegg AE (1983) Assay of aminopropyltransferases. Methods Enzymol 94:260–265PubMedCrossRefGoogle Scholar
  24. 24.
    Pegg AE, Williams-Ashman HG (1969) Phosphate-stimulated breakdown of 5′-methylthioadenosine by rat ventral prostate. Biochem J 115:241–247PubMedGoogle Scholar
  25. 25.
    Albers E (2009) Metabolic characteristics and importance of the universal methionine salvage pathway recycling methionine from 5′-methylthioadenosine. IUBMB Life 61:1132–1142PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Charles E. Schwartz
    • 1
    Email author
  • Xaiojing Wang
    • 2
  • Roger E. Stevenson
    • 1
  • Anthony E. Pegg
    • 3
  1. 1.Greenwood Genetic CenterJ.C. Self Research InstituteGreenwoodUSA
  2. 2.Department of Cellular and Molecular Physiology, Milton S. Hershey Medical CenterPennsylvania State University College of MedicineHersheyUSA
  3. 3.College of Medicine, Milton S. Hershey Medical CenterPennsylvania State UniversityHersheyUSA

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