Arylsulfatase A Explained

Arylsulfatase A (or cerebroside-sulfatase) is an enzyme that breaks down sulfatides, namely cerebroside 3-sulfate into cerebroside and sulfate. In humans, arylsulfatase A is encoded by the ARSA gene.^{[1] [2]}

Clinical significance

A deficiency in Arylsulfatase A is associated with metachromatic leukodystrophy, an autosomal recessive disease.^[3] Multiple sulfatase deficiency (MSD) is also associated with the ARSA gene.^[4]

Biochemistry

Enzyme regulation

Arylsulfatase A is inhibited by phosphate, which forms a covalent bond with the active site 3-oxoalanine.^[5]

Further reading

• Narahara K . Terminal 22q deletion associated with a partial deficiency of arylsulphatase A . J. Med. Genet. . 29 . 6 . 432–3 . 1992 . 1352356 . 10.1136/jmg.29.6.432 . 1016000 . vanc. Takahashi Y . Murakami M . 3 . Tsuji . K . Yokoyama . Y . Murakami . R . Ninomiya . S . Seino . Y .
• Gieselmann V . Molecular genetics of metachromatic leukodystrophy . Hum. Mutat. . 4 . 4 . 233–42 . 1995 . 7866401 . 10.1002/humu.1380040402 . vanc. Zlotogora J . Harris A . 3 . Wenger . David A . Morris . C Phillip . 23519007 . free .
• DeLuca C, Brown JA, Shows TB . Lysosomal arylsulfatase deficiencies in humans: Chromosome assignments for arylsulfatase A and B . Proc. Natl. Acad. Sci. U.S.A. . 76 . 4 . 1957–61 . 1979 . 36611 . 10.1073/pnas.76.4.1957 . 383512 . 1979PNAS...76.1957D . free .
• Fujii T . Proteolytic processing of human lysosomal arylsulfatase A . Biochim. Biophys. Acta . 1122 . 1 . 93–8 . 1992 . 1352993 . 10.1016/0167-4838(92)90132-W . vanc. Kobayashi T . Honke K . 3 . Gasa . S . Ishikawa . M . Shimizu . T . Makita . A .
• Kappler J, von Figura K, Gieselmann V . Late-onset metachromatic leukodystrophy: molecular pathology in two siblings . Ann. Neurol. . 31 . 3 . 256–61 . 1992 . 1353340 . 10.1002/ana.410310305 . 5481565 .
• Li ZG, Waye JS, Chang PL . Diagnosis of arylsulfatase A deficiency . Am. J. Med. Genet. . 43 . 6 . 976–82 . 1992 . 1357970 . 10.1002/ajmg.1320430614 .
• Polten A . Molecular basis of different forms of metachromatic leukodystrophy . N. Engl. J. Med. . 324 . 1 . 18–22 . 1991 . 1670590 . 10.1056/NEJM199101033240104 . vanc. Fluharty AL . Fluharty CB . 3 . Kappler . Joachim . Von Figura . Kurt . Gieselmann . Volkmar . free .
• Kondo R . Identification of a mutation in the arylsulfatase A gene of a patient with adult-type metachromatic leukodystrophy . Am. J. Hum. Genet. . 48 . 5 . 971–8 . 1991 . 1673291 . 1683039 . vanc. Wakamatsu N . Yoshino H . 3 . Fukuhara . N . Miyatake . T . Tsuji . S .
• Nelson PV, Carey WF, Morris CP . Population frequency of the arylsulphatase A pseudo-deficiency allele . Hum. Genet. . 87 . 1 . 87–8 . 1991 . 1674719 . 10.1007/BF01213099 . 12287382 .
• Bohne W, von Figura K, Gieselmann V . An 11-bp deletion in the arylsulfatase A gene of a patient with late infantile metachromatic leukodystrophy . Hum. Genet. . 87 . 2 . 155–8 . 1991 . 1676699 . 10.1007/BF00204172 . 21529779 .
• Gieselmann V, Fluharty AL, Tønnesen T, Von Figura K . Mutations in the arylsulfatase A pseudodeficiency allele causing metachromatic leukodystrophy . Am. J. Hum. Genet. . 49 . 2 . 407–13 . 1991 . 1678251 . 1683316 .
• Fluharty AL . Two new arylsulfatase A (ARSA) mutations in a juvenile metachromatic leukodystrophy (MLD) patient . Am. J. Hum. Genet. . 49 . 6 . 1340–50 . 1992 . 1684088 . 1686463 . vanc. Fluharty CB . Bohne W . 3 . Von Figura . K . Gieselmann . V .
• Kreysing J, von Figura K, Gieselmann V . Structure of the arylsulfatase A gene . Eur. J. Biochem. . 191 . 3 . 627–31 . 1990 . 1975241 . 10.1111/j.1432-1033.1990.tb19167.x .
• Gieselmann V, Polten A, Kreysing J, von Figura K . Arylsulfatase A pseudodeficiency: loss of a polyadenylylation signal and N-glycosylation site . Proc. Natl. Acad. Sci. U.S.A. . 86 . 23 . 9436–40 . 1990 . 2574462 . 10.1073/pnas.86.23.9436 . 298511 . free .
• Geurts van Kessel AH . Regional localization of the genes coding for human ACO2, ARSA, and NAGA on chromosome 22 . Cytogenet. Cell Genet. . 28 . 3 . 169–72 . 1981 . 7192199 . 10.1159/000131527.
• Barth ML, Fensom A, Harris A . Identification of seven novel mutations associated with metachromatic leukodystrophy . Hum. Mutat. . 6 . 2 . 170–6 . 1995 . 7581401 . 10.1002/humu.1380060210 . 27966734 . free .
• Schmidt B, Selmer T, Ingendoh A, von Figura K . A novel amino acid modification in sulfatases that is defective in multiple sulfatase deficiency . Cell . 82 . 2 . 271–8 . 1995 . 7628016 . 10.1016/0092-8674(95)90314-3 . free .
• Barth ML . Frequency of arylsulphatase A pseudodeficiency associated mutations in a healthy population . J. Med. Genet. . 31 . 9 . 667–71 . 1995 . 7815433 . 10.1136/jmg.31.9.667 . 1050073 . vanc. Ward C . Harris A . 3 . Saad . A . Fensom . A .

External links

• GeneReviews/NCBI/NIH/UW entry on Arylsulfatase A Deficiency - Metachromatic Leukodystrophy
• OMIM entries on ARSA Deficiency

Notes and References

1. Stein C, Gieselmann V, Kreysing J, Schmidt B, Pohlmann R, Waheed A, Meyer HE, O'Brien JS, von Figura K . Cloning and expression of human arylsulfatase A . J. Biol. Chem. . 264 . 2 . 1252–9 . January 1989 . 10.1016/S0021-9258(19)85079-2 . 2562955 . free .
2. Matzner U, Herbst E, Hedayati KK, Lüllmann-Rauch R, Wessig C, Schröder S, Eistrup C, Möller C, Fogh J, Gieselmann V . Enzyme replacement improves nervous system pathology and function in a mouse model for metachromatic leukodystrophy . Hum. Mol. Genet. . 14 . 9 . 1139–52 . May 2005 . 15772092 . 10.1093/hmg/ddi126 . free .
3. Sevin C, Aubourg P, Cartier N . Enzyme, cell and gene-based therapies for metachromatic leukodystrophy . J. Inherit. Metab. Dis. . 30 . 2 . 175–83 . April 2007 . 17347913 . 10.1007/s10545-007-0540-z . 25848916 .
4. Web site: UniProt . 2023-10-31 . www.uniprot.org.
5. Web site: Sino Biological. Arylsulfatase A / ARSA. 12 September 2014.