GLA hydrolyzes PSAP(195-273):Gal2Cer:PE

Stable Identifier
Reaction [transition]
Homo sapiens
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Alpha-galactosidase A (GLA) (Bishop et al. 1986) removes the terminal galactose residue from glycolipids or glycoproteins, mobilized by PSAP(195-273) (Saposin B), resulting in galactose and an alcohol. An example is the Fabry disease substrate digalactosylceramide (Gal2Cer) which is hydrolysed to form galactose and galactosylceramide (GalCer) (Dean & Sweeley, 1979). GLA functions as a homodimer (Garman & Garboczi 2004) and defects in this enzyme lead to Fabry disease (FD) (MIM:301500), a rare X-linked sphingolipidosis disease where glycolipids such as Gal2Cer accumulate in many tissues (Garman & Garboczi 2004, Eng et al. 1993, Shabeer et al. 2006). Researchers also observed elevated Gal2Cer in prosaposin deficiency (PSAPD, MIM: 611721) cases, a rare disease with low levels of all saposins. Saposin B (PSAP(195-273)) is an essential cofactor to the reaction (Bradova et al., 1993; Kase et al., 1996)
Literature References
PubMed ID Title Journal Year
15003450 The molecular defect leading to Fabry disease: structure of human alpha-galactosidase

Garman, SC, Garboczi, DN

J Mol Biol 2004
16595074 Fabry disease: identification of 50 novel alpha-galactosidase A mutations causing the classic phenotype and three-dimensional structural analysis of 29 missense mutations

Yasuda, M, Shabbeer, J, Benson, SD, Desnick, RJ

Hum Genomics 2006
7504405 Nature and frequency of mutations in the alpha-galactosidase A gene that cause Fabry disease

Resnick-Silverman, LA, Eng, CM, Desnick, RJ, Astrin, KH, Niehaus, DJ

Am J Hum Genet 1993
8370580 Prosaposin deficiency: further characterization of the sphingolipid activator protein-deficient sibs. Multiple glycolipid elevations (including lactosylceramidosis), partial enzyme deficiencies and ultrastructure of the skin in this generalized sphingolipid storage disease

Paton, BC, Harzer, K, Smíd, F, Bradová, V, Ulrich-Bott, B, Roggendorf, W

Hum Genet 1993
39940 Studies on human liver alpha-galactosidases. I. Purification of alpha-galactosidase A and its enzymatic properties with glycolipid and oligosaccharide substrates

Dean, KJ, Sweeley, CC

J Biol Chem 1979
8804427 Only sphingolipid activator protein B (SAP-B or saposin B) stimulates the degradation of globotriaosylceramide by recombinant human lysosomal alpha-galactosidase in a detergent-free liposomal system

Suzuki, M, Klein, A, Kolter, T, Sakuraba, H, Hashimoto, Y, Kase, R, Itoh, K, Bierfreund, U, Sandhoff, K

FEBS Lett 1996
3014515 Human alpha-galactosidase A: nucleotide sequence of a cDNA clone encoding the mature enzyme

Hantzopoulos, P, Bernstein, HS, Desnick, RJ, Calhoun, DH, Bishop, DF, Quinn, M

Proc Natl Acad Sci U S A 1986
Catalyst Activity

alpha-galactosidase activity of GLA dimer [lysosomal lumen]

Orthologous Events
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