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ARSA  -  arylsulfatase A

Homo sapiens

Synonyms: ASA, Arylsulfatase A, Cerebroside-sulfatase
 
 
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Disease relevance of ARSA

 

Psychiatry related information on ARSA

  • The aim of this study was to establish frequency of two mutations associated with ASA pseudodeficiency in healthy individuals in the Croatian population as well as in persons with Alzheimer-type dementia and Down syndrome [6].
  • Arylsulfatase A activity was slightly but not significantly decreased in leukocytes derived from subjects with dementia and Down syndrome in comparison with age-matched control samples [6].
  • A previous case report has suggested an association with mild-to-moderate deficiency of arylsulfatase A. We describe a 36-year-old man who recovered completely from an episode of hypoxia related to drug overdose, and 2 weeks later progressed from a confusional state to deep coma [7].
 

High impact information on ARSA

  • To understand the molecular basis of the different forms of the disease, we analyzed arylsulfatase A alleles associated with metachromatic leukodystrophy [8].
  • The clinical variability can be explained by the different levels of residual arylsulfatase A activity associated with these genotypes [8].
  • We show that selective degeneration of hippocampal neurons is a central step in disease pathogenesis, and provide evidence that in vivo transfer of ARSA by lentiviral vectors reverts the disease phenotype in all investigated areas [9].
  • Arylsulfatase A and B activities were found to be reduced in the presence of ascorbic acid in all normal and osteoarthritic cell lines examined when measured 3, 6, 10, and 13 days after the introduction of the vitamin in the culture medium [10].
  • Arylsulfatase B was separated from arylsulfatase A in extracts of human lung tissue by anion exchange chromatography and further purified by gel filtration and cation exchange chromatography [11].
 

Chemical compound and disease context of ARSA

 

Biological context of ARSA

 

Anatomical context of ARSA

 

Associations of ARSA with chemical compounds

  • In contrast to alleles that cause early-onset MLD, the arginine84 to glutamine substitution is associated with some residual ARSA activity [16].
  • It is proposed that histidine 229 protonates the leaving alcoholate after hydrolysis.C69S-ASA is able to bind covalently to the substrate and hydrolyze it, but is unable to release the resulting sulfate [21].
  • Arylsulfatase A (ASA) belongs to the sulfatase family whose members carry a C(alpha)-formylglycine that is post-translationally generated by oxidation of a conserved cysteine or serine residue [21].
  • This suggests that the double conformation observed in the structure of wild-type ASA is more likely to correspond to a formylglycine hydrate than to a twofold disordered aldehyde oxo group, and accounts for the relative inertness of the C69S-ASA mutant [21].
  • The structure of C69S-ASA shows the serine side-chain in a single conformation, turned away from the position a substrate occupies in the complex [21].
 

Regulatory relationships of ARSA

  • Furthermore, the uptake of the lysosomal enzyme arylsulfatase A and of a Man-6-P neoglycoprotein is stimulated 2-3-fold by IGF I and IGF II, and this effect persists for at least 6 h [22].
 

Other interactions of ARSA

  • Among the recombinant enzymes only the endoplasmic reticulum-associated ARSC showed activity toward iodothyronine sulfates; the soluble lysosomal ARSA and ARSB were inactive [23].
  • One cosmid, representing a region coding for an ubiquitous 300-bp transcript, is localized 600 kb from PDGFB, and four cosmids contained sequences surrounding the ARSA gene at 22q13 [24].
  • Regional localization of the genes coding for human ACO2, ARSA, and NAGA on chromosome 22 [19].
  • The results suggest the assignment of ARSA and NAGA to the region 22q13 leads to 22qter and of ACO2 to the region 22q11 leads to 22q13 [19].
  • The human genome contains six arylsulfatase genes (ARSA-ARSF), of which four are clustered in a distal region of the short arm of the X chromosome (Xp22.3) [25].
 

Analytical, diagnostic and therapeutic context of ARSA

References

  1. High residual arylsulfatase A (ARSA) activity in a patient with late-infantile metachromatic leukodystrophy. Kreysing, J., Bohne, W., Bösenberg, C., Marchesini, S., Turpin, J.C., Baumann, N., von Figura, K., Gieselmann, V. Am. J. Hum. Genet. (1993) [Pubmed]
  2. Adult onset metachromatic leukodystrophy without electroclinical peripheral nervous system involvement: a new mutation in the ARSA gene. Marcão, A.M., Wiest, R., Schindler, K., Wiesmann, U., Weis, J., Schroth, G., Miranda, M.C., Sturzenegger, M., Gieselmann, V. Arch. Neurol. (2005) [Pubmed]
  3. Homozygote for mutation c.1204 + 1G > A of the ARSA gene presents with a late-infantile form of metachromatic leukodystrophy and a rare MRI white matter lesion type. Ługowska, A., Szymańska, K., Kmiec, T., Tarczyńska, I., Czartoryska, B., Tylki-Szymańska, A., Jurkiewicz, E. J. Appl. Genet. (2005) [Pubmed]
  4. Molecular genetics of metachromatic leukodystrophy. Gieselmann, V., Zlotogora, J., Harris, A., Wenger, D.A., Morris, C.P. Hum. Mutat. (1994) [Pubmed]
  5. Metachromatic leukodystrophy: identification of the first deletion in exon 1 and of nine novel point mutations in the arylsulfatase A gene. Draghia, R., Letourneur, F., Drugan, C., Manicom, J., Blanchot, C., Kahn, A., Poenaru, L., Caillaud, C. Hum. Mutat. (1997) [Pubmed]
  6. Croatian population data for arylsulfatase a pseudodeficiency-associated mutations in healthy subjects, and in patients with Alzheimer-type dementia and Down syndrome. Bognar, S.K., Furac, I., Kubat, M., Cosović, C., Demarin, V. Arch. Med. Res. (2002) [Pubmed]
  7. Delayed posthypoxic demyelination. Association with arylsulfatase A deficiency and lactic acidosis on proton MR spectroscopy. Gottfried, J.A., Mayer, S.A., Shungu, D.C., Chang, Y., Duyn, J.H. Neurology (1997) [Pubmed]
  8. Molecular basis of different forms of metachromatic leukodystrophy. Polten, A., Fluharty, A.L., Fluharty, C.B., Kappler, J., von Figura, K., Gieselmann, V. N. Engl. J. Med. (1991) [Pubmed]
  9. In vivo gene therapy of metachromatic leukodystrophy by lentiviral vectors: correction of neuropathology and protection against learning impairments in affected mice. Consiglio, A., Quattrini, A., Martino, S., Bensadoun, J.C., Dolcetta, D., Trojani, A., Benaglia, G., Marchesini, S., Cestari, V., Oliverio, A., Bordignon, C., Naldini, L. Nat. Med. (2001) [Pubmed]
  10. Effect of ascorbic acid on arylsulfatase activities and sulfated proteoglycan metabolism in chondrocyte cultures. Schwartz, E.R., Adamy, L. J. Clin. Invest. (1977) [Pubmed]
  11. Arylsulfatase B of human lung. Isolation, characterization, and interaction with slow-reacting substance of anaphylaxis. Wasserman, S.I., Austen, K.F. J. Clin. Invest. (1976) [Pubmed]
  12. An adult-type metachromatic leukodystrophy caused by substitution of serine for glycine-122 in arylsulfatase A. Honke, K., Kobayashi, T., Fujii, T., Gasa, S., Xu, M., Takamaru, Y., Kondo, R., Tsuji, S., Makita, A. Hum. Genet. (1993) [Pubmed]
  13. A missense mutation P136L in the arylsulfatase A gene causes instability and loss of activity of the mutant enzyme. Kafert, S., Heinisch, U., Zlotogora, J., Gieselmann, V. Hum. Genet. (1995) [Pubmed]
  14. Measurements from normal umbilical cord blood of four lysosomal enzymatic activities: alpha-L-iduronidase (Hurler), galactocerebrosidase (globoid cell leukodystrophy), arylsulfatase A (metachromatic leukodystrophy), arylsulfatase B (Maroteaux-Lamy). deGasperi, R., Raghavan, S.S., Sosa, M.G., Kolodny, E.H., Carrier, C., Rubenstein, P., Peters, C., Wagner, J., Kurtzberg, J., Krivit, W. Bone Marrow Transplant. (2000) [Pubmed]
  15. Arylsulfatases A and B in EBV-transformed lymphoid cell lines: studies on their molecular forms in cells from patients with inborn sulfatase deficiencies. Comparative diagnostic value of enzymatic assays. Tempesta, M.C., Levade, T., Salvayre, R. Clin. Chim. Acta (1991) [Pubmed]
  16. Late-onset metachromatic leukodystrophy: molecular pathology in two siblings. Kappler, J., von Figura, K., Gieselmann, V. Ann. Neurol. (1992) [Pubmed]
  17. An arylsulfatase A (ARSA) missense mutation (T274M) causing late-infantile metachromatic leukodystrophy. Harvey, J.S., Nelson, P.V., Carey, W.F., Robertson, E.F., Morris, C.P. Hum. Mutat. (1993) [Pubmed]
  18. The genes for the highly homologous Ca(2+)-binding proteins oncomodulin and parvalbumin are not linked in the human genome. Ritzler, J.M., Sawhney, R., Geurts van Kessel, A.H., Grzeschik, K.H., Schinzel, A., Berchtold, M.W. Genomics (1992) [Pubmed]
  19. Regional localization of the genes coding for human ACO2, ARSA, and NAGA on chromosome 22. Geurts van Kessel, A.H., Westerveld, A., de Groot, P.G., Meera Khan, P., Hagemeijer, A. Cytogenet. Cell Genet. (1980) [Pubmed]
  20. Three-dimensional structures of sulfatases. Ghosh, D. Meth. Enzymol. (2005) [Pubmed]
  21. Crystal structure of an enzyme-substrate complex provides insight into the interaction between human arylsulfatase A and its substrates during catalysis. von Bülow, R., Schmidt, B., Dierks, T., von Figura, K., Usón, I. J. Mol. Biol. (2001) [Pubmed]
  22. Insulin-like growth factors I and II stimulate endocytosis but do not affect sorting of lysosomal enzymes in human fibroblasts. Braulke, T., Tippmer, S., Chao, H.J., von Figura, K. J. Biol. Chem. (1990) [Pubmed]
  23. Characterization of iodothyronine sulfatase activities in human and rat liver and placenta. Kester, M.H., Kaptein, E., Van Dijk, C.H., Roest, T.J., Tibboel, D., Coughtrie, M.W., Visser, T.J. Endocrinology (2002) [Pubmed]
  24. Cosmid-derived transcripts and sequence tags mapped to three subregions of human chromosome 22. Pusch, C., Müllenbach, R., Gött, P., Schmitt, H., Wang, Z., Roe, B., Blin, N. Gene (1996) [Pubmed]
  25. Arylsulfatase D gene in Xp22.3 encodes two protein isoforms. Urbitsch, P., Salzer, M.J., Hirschmann, P., Vogt, P.H. DNA Cell Biol. (2000) [Pubmed]
  26. Coincidence of two novel arylsulfatase A alleles and mutation 459+1G>A within a family with metachromatic leukodystrophy: molecular basis of phenotypic heterogeneity. Berger, J., Gmach, M., Mayr, U., Molzer, B., Bernheimer, H. Hum. Mutat. (1999) [Pubmed]
  27. Metachromatic leukodystrophy in the Navajo Indian population: a splice site mutation in intron 4 of the arylsulfatase A gene. Pastor-Soler, N.M., Rafi, M.A., Hoffman, J.D., Hu, D., Wenger, D.A. Hum. Mutat. (1994) [Pubmed]
  28. Influences of breathing patterns on respiratory sinus arrhythmia in humans during exercise. Blain, G., Meste, O., Bermon, S. Am. J. Physiol. Heart Circ. Physiol. (2005) [Pubmed]
  29. Mutations c.459+1G>A and p.P426L in the ARSA gene: prevalence in metachromatic leukodystrophy patients from European countries. Lugowska, A., Amaral, O., Berger, J., Berna, L., Bosshard, N.U., Chabas, A., Fensom, A., Gieselmann, V., Gorovenko, N.G., Lissens, W., Mansson, J.E., Marcao, A., Michelakakis, H., Bernheimer, H., Ol'khovych, N.V., Regis, S., Sinke, R., Tylki-Szymanska, A., Czartoryska, B. Mol. Genet. Metab. (2005) [Pubmed]
  30. Metabolic correction in oligodendrocytes derived from metachromatic leukodystrophy mouse model by using encapsulated recombinant myoblasts. Consiglio, A., Martino, S., Dolcetta, D., Cusella, G., Conese, M., Marchesini, S., Benaglia, G., Wrabetz, L., Orlacchio, A., Déglon, N., Aebischer, P., Severini, G.M., Bordignon, C. J. Neurol. Sci. (2007) [Pubmed]
 
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