Reactome | ARSA removes sulfate from PSAP(195-273):Sulfatide

ARSA removes sulfate from PSAP(195-273):Sulfatide

Stable Identifier

R-HSA-1606807

Type

Reaction [transition]

Species

Homo sapiens

Compartment

lysosomal lumen

ReviewStatus

5/5

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ARSA removes sulfate from PSAP(195-273):Sulfatide

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Arylsulfatase A (ARSA) hydrolyses a sulfatide (cerebroside 3-sulfate, SM4) to form a cerebroside and sulfate Stinshoff & Jatzkewitz, 1975). Saposin B (PSAP(195-273)) is a promiscuous lipid-binding and transfer protein and an essential cofactor for the lysosomal hydrolysis of sulfatide by ARSA. It binds sulfatides in soluble stoichiometric complexes, which ARSA recognizes as substrates (Fischer & Jatzkewitz, 1975). ARSA is present in the lysosomal lumen and comprises two chains, components B and C, linked by disulfide bonds (Stein et al. 1989, 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 metachromatic leukodystrophy (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). In metachromatic leukodystrophy due to saposin B deficiency (MLDSAPB, MIM:249290) sulfatide accumulates because of the missing cofactor saposin B (Regis et al., 1999).

Literature References

PubMed ID	Title	Journal	Year
239890	The activator of cerebroside sulphatase. Purification from human liver and identification as a protein Jatzkewitz, H, Fischer, G	Hoppe Seylers Z Physiol Chem	1975
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
235289	Comparison of the cerebroside sulphatase and the arylsulphatase activity of human sulphatase A in the absence of activators Stinshoff, K, Jatzkewitz, H	Biochim Biophys Acta	1975
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
10196694	An Asn > Lys substitution in saposin B involving a conserved amino acidic residue and leading to the loss of the single N-glycosylation site in a patient with metachromatic leukodystrophy and normal arylsulphatase A activity Gatti, R, Caroli, F, Keulemans, JL, van Diggelen, OP, Corsolini, F, Filocamo, M, Regis, S	Eur J Hum Genet	1999
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, Tønnesen, 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