Reactome | NEU1,4 hydrolyze PSAP(195-273):GM3:PE

NEU1,4 hydrolyze PSAP(195-273):GM3:PE

Stable Identifier

R-HSA-1605724

Type

Reaction [transition]

Species

Homo sapiens

Compartment

lysosomal lumen

ReviewStatus

5/5

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Ganglioside GM3, mobilized by Saposin B (PSAP(195-273)), is hydrolyzed by sialidases to lactosylceramide (LacCer). Sialidases (NEU, neuraminidases) hydrolyze sialic acids (N-acetylneuramic acid, Neu5Ac, NANA) to produce asialo compounds, a step in the degradation process of glycoproteins and gangliosides. NEU1 and NEU4 hydrolyse NANA in the lysosomal lumen. NEU1 is active in a multienzyme complex comprising cathepsin A protective protein (CTSA) and beta-galactosidase (Bonten et al. 1996, Rudenko et al. 1995). Defects in NEU1 cause Sialidosis (MIM:256550) (Bonten et al. 1996). CTSA appears to exert a protective function necessary for the stability and activity of these enzymes (Galjart et al. 1988). Defects in CTSA are the cause of galactosialidosis (GSL, MIM:256540) (Zhou et al. 1991). NEU4 is also a lysosomal sialidase which, unlike NEU1, does not require association with other proteins for enzymatic activity. Isoform 2 seems to be the lysosomal sialidase (Seyrantepe et al. 2004). Researchers observed elevated GM3 in prosaposin deficiency (PSAPD, MIM: 611721) cases, a rare disease with low levels of all saposins. The essential cofactor missing appears to be Saposin B (PSAP(195-273)) (Schmidt et al., 1992; Bradova et al., 1993).

Literature References

PubMed ID	Title	Journal	Year
1634229	Metabolism of GM1 ganglioside in cultured skin fibroblasts: anomalies in gangliosidoses, sialidoses, and sphingolipid activator protein (SAP, saposin) 1 and prosaposin deficient disorders Schmid, B, Paton, BC, Sandhoff, K, Harzer, K	Hum Genet	1992
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
15213228	Neu4, a novel human lysosomal lumen sialidase, confers normal phenotype to sialidosis and galactosialidosis cells Seyrantepe, V, Landry, K, Trudel, S, Hassan, JA, Morales, CR, Pshezhetsky, AV	J Biol Chem	2004
8591035	Three-dimensional structure of the human 'protective protein': structure of the precursor form suggests a complex activation mechanism Rudenko, G, Bonten, E, d'Azzo, A, Hol, WG	Structure	1995
1756715	A mutation in a mild form of galactosialidosis impairs dimerization of the protective protein and renders it unstable Zhou, XY, Galjart, NJ, Willemsen, R, Gillemans, N, Galjaard, H, d'Azzo, A	EMBO J	1991
8985184	Characterization of human lysosomal neuraminidase defines the molecular basis of the metabolic storage disorder sialidosis Bonten, E, van der Spoel, A, Fornerod, M, Grosveld, G, d'Azzo, A	Genes Dev	1996
3136930	Expression of cDNA encoding the human "protective protein" associated with lysosomal beta-galactosidase and neuraminidase: homology to yeast proteases Galjart, NJ, Gillemans, N, Harris, A, van der Horst, GT, Verheijen, FW, Galjaard, H, d'Azzo, A	Cell	1988