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

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

Stable Identifier

R-HSA-9841189

Type

Reaction [transition]

Species

Homo sapiens

Compartment

lysosomal lumen

ReviewStatus

5/5

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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 Shabbeer, J, Yasuda, M, Benson, SD, Desnick, RJ	Hum Genomics	2006
7504405	Nature and frequency of mutations in the alpha-galactosidase A gene that cause Fabry disease Eng, CM, Resnick-Silverman, LA, Niehaus, DJ, Astrin, KH, Desnick, RJ	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 Bradová, V, Smíd, F, Ulrich-Bott, B, Roggendorf, W, Paton, BC, Harzer, K	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 Kase, R, Bierfreund, U, Klein, A, Kolter, T, Itoh, K, Suzuki, M, Hashimoto, Y, Sandhoff, K, Sakuraba, H	FEBS Lett	1996
3014515	Human alpha-galactosidase A: nucleotide sequence of a cDNA clone encoding the mature enzyme Bishop, DF, Calhoun, DH, Bernstein, HS, Hantzopoulos, P, Quinn, M, Desnick, RJ	Proc Natl Acad Sci U S A	1986