Fabry disease is a sphingolipid storage disorder resulting from a deficiency of the lysosomal hydrolase, α-galactosidase A. The deficiency leads to lysosomal accumulation of α-galactosidase A substrates, neutral glycosphingolipids with terminal α-galactosyl moieties, in multiple tissues. Globotriaosylceramide (Gb3Cer, CD77), the critical substrate of α-galactosidase A, is involved in cell signaling and associates itself with lipid rafts in the plasma membrane, where it also functions as a receptor for the Shiga-like toxins of E. Coli. Possible roles of Gb3Cer accumulation in the pathogenesis of Fabry disease, as well as biochemistry and function of minor α-galactosidase A substrates are discussed. There are two human lysosomal enzymes with the ability to hydrolyze substrates with terminal α-galactose, α-galactosidase A and α-N-acetylgalactosaminidase (NAGA). Both enzymes are active in vitro against saccharide, glycolipid and artificial substrates. α-N-acetylgalactosaminidase's primary function appears to be hydrolysis of acetylated oligosaccharides and glycopeptides, while α-galactosidase A is the enzyme responsible for degradation of glycolipid substrates. α-Galactosidase A requires an activator protein, saposin B, for its activity in vivo. Properties of the above proteins and the biochemistry of their deficiencies in humans are also addressed. © 2010 Springer Science+Business Media B.V.
CITATION STYLE
Hřebíček, M., & Ledvinová, J. (2010). Biochemistry of fabry disease. In Fabry Disease (pp. 81–104). Springer Netherlands. https://doi.org/10.1007/978-90-481-9033-1_4
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