Reactome | GLA hydrolyzes PSAP(195-273):Gb3Cer:PE

GLA hydrolyzes PSAP(195-273):Gb3Cer:PE

Stable Identifier

R-HSA-1605736

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 globotriaosylceramide (Gb3Cer) which is hydrolysed to form galactose and lactosylceramide. 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 Gb3Cer accumulate in many tissues (Garman & Garboczi 2004, Eng et al. 1993, Shabeer et al. 2006). Researchers also observed elevated Gb3Cer 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).

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
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