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Glycosphingolipid Activator Proteins

  • W. Fürst
  • A. Vogel
  • M. Lee-Vaupel
  • E. Conzelmann
  • K. Sandhoff
Part of the NATO ASI Series book series (NSSA, volume 116)

Abstract

The catabolism of sphingolipids is accomplished in the intracellular digestive vacuoles known as lysosomes by the sequential action of acid exohydrolases, starting at the hydrophilic end of the molecule. For nearly every degradation step an inherited enzyme deficiency is known leading to a severe sphingolipid storage disease. In the last 20 years intensive studies were performed in many laboratories to understand the molecular basis and the increasing heterogeneity of these disorders (1–6). The lysosomal hydrolases involved in glycolipid degradation have been purified and characterized. Some of these enzymes are membrane-bound whereas others are water-soluble. When the degradation of the presumtive glycosphingolipid substrates by purified soluble enzymes was studied in vitro, only low, often negligible degradation rates were observed. Since sphingolipids are amphiphilic molecules, they form micelles (higher glycosylated glycolipids) or liposomes (sphingomyelin) when dispersed in water. In this tightly packed form, they are hardly accessible to the purified hydrolases.An enormous stimulation of the enzymic hydrolysis can be achieved by the addition of suitable detergents, such as bile salts (3, 7). At appropriate concentrations, detergents and glycolipids form small mixed micelles from which the oligosaccharide chains protrude far enough to be attacked by the hydrolases. However, these detergent-based assay mixtures do not reflect the in vivo situation, since lysosomes do not contain detergents. The interaction between lysosomal, water-soluble hydrolases and their membrane-bound glycolipid substrates must be brought about in some other way. Since 1964 several non-enzymic protein factors, called activators, have been described, which perform this function and thus accelerate the enzymic degradation of glycosphingolipids.

Keywords

Sialic Acid Activator Protein Lipid Substrate Metachromatic Leukodystrophy Sandhoff Disease 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • W. Fürst
    • 1
  • A. Vogel
    • 1
  • M. Lee-Vaupel
    • 1
  • E. Conzelmann
    • 1
  • K. Sandhoff
    • 1
  1. 1.Institut für Organische Chemie und BiochemieUniversität BonnBonn 1Germany

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