Arylsulfatase A hydrolyses sulfate from sulfatide to form cerebroside

Stable Identifier
Reaction [transition]
Homo sapiens
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Arylsulfatase A (ARSA) (Stein et al. 1989) hydrolyses a sulfatide (a cerebroside 3-sulfate) to form a cerebroside and sulfate. ARSA is present in the lysosomal lumen and comprises two chains, component B and C linked by disulphide bonds (Fujii et al. 1992). The conversion to 3-oxoalanine (formylglycine, FGly) of a cysteine residue is critical for catalytic activity in all eukaryotes (Chruszcz et al. 2003, Lukatela et al. 1998).
Defects in ARSA are a cause of leukodystrophy metachromatic (MLD) (MIM:250100), characterized by lysosomal storage of cerebroside-3-sulfate in neural and non-neural tissues (Gieselmann et al. 1991, Polten et al. 1991). Arylsulfatase A activity is reduced in multiple sulfatase deficiency (MSD) (MIM:272200), a disorder characterized by decreased activity of sulfatases. The defect is due to the lack of post-translational modification of the critical cysteine needed for activity (Schmidt et al. 1995).

Literature References
PubMed ID Title Journal Year
1670590 Molecular basis of different forms of metachromatic leukodystrophy

Polten, A, Kappler, J, Gieselmann, V, Fluharty, AL, von Figura, K, Fluharty, CB

N Engl J Med 1991
2562955 Cloning and expression of human arylsulfatase A

Pohlmann, R, Stein, C, Gieselmann, V, O'Brien, JS, Meyer, HE, von Figura, K, Waheed, A, Kreysing, J, Schmidt, B

J Biol Chem 1989
9521684 Crystal structure of human arylsulfatase A: the aldehyde function and the metal ion at the active site suggest a novel mechanism for sulfate ester hydrolysis

Krauss, N, Selmer, T, Gieselmann, V, Saenger, W, von Figura, K, Lukatela, G, Theis, K

Biochemistry 1998
1352993 Proteolytic processing of human lysosomal arylsulfatase A

Gasa, S, Makita, A, Shimizu, T, Kobayashi, T, Fujii, T, Honke, K, Ishikawa, M

Biochim Biophys Acta 1992
7628016 A novel amino acid modification in sulfatases that is defective in multiple sulfatase deficiency

Selmer, T, Ingendoh, A, von Figura, K, Schmidt, B

Cell 1995
1678251 Mutations in the arylsulfatase A pseudodeficiency allele causing metachromatic leukodystrophy

Gieselmann, V, Fluharty, AL, von Figura, K, T√łnnesen, T

Am J Hum Genet 1991
12888274 Crystal structure of a covalent intermediate of endogenous human arylsulfatase A

Lebioda, L, Lewinski, K, Laidler, P, Ortlund, E, Monkiewicz, M, Chruszcz, M

J Inorg Biochem 2003
Catalyst Activity

cerebroside-sulfatase activity of active ARSA:Ca2+ [lysosomal lumen]

Orthologous Events
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