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Studies of SAP-1 and SAP-2 in Cultured Skin Fibroblasts

  • David A. Wenger
  • Shinsuke Fujibayashi
Part of the NATO ASI Series book series (NSSA, volume 116)

Abstract

Sphingolipid activator proteins (SAP) are relatively small molecular weight proteins that activate the hydrolysis of sphingolipids in the presence of the specific lysosomal hydrolases.l The exact number of such proteins and their exact mechanisms of action are not known at this time. However, three proteins with the ability to stimulate the enzymatic hydrolysis of certain sphingolipids have been identified. By our nomenclature SAP-1 has been demonstrated to activate the hydrolysis of sulfatide, GM1 ganglioside and, possibly, globotriaosylceramide by arylsulfatase A, acid β ß-galactosidase and α-galactodidase A, respectively.2–6 SAP-1 is missing in tissue and urine samples from patients with a variant form of metachromatic leukodystrophy.7–10 SAP-2 (factor P, heat-stable factor, cohydrolase SPHI) activates the enzymatic hydrolysis of glucosylceramide (glc-cer), galactosylceramide (gal-cer) and, possibly, sphingomyelin by glucocerebrosi-dase, galactocerebrosidase and sphingomyelinase, respectively.11–15 SAP-2 appears to be normal in tissue samples and fibroblast extracts from patients with Gaucher disease, Krabbe disease and Niemann-Pick disease (including Type C).16 SAP-3 (GM2 activator protein) stimulates the enzymatic hydrolysis of GM2 ganglioside by hexosaminidase A. 17,18 It is deficient in tissue samples and cultured cells from patients with the AB variant form of GM2 gangliosidosis.18–20 There has been some discrepancy about the sizes of native and denatured SAP. In order to learn more about the structure of SAP-1 and SAP-2, their mechanism of action and the nature of the mutations in patients with SAP-1 deficiency the structure and biosynthesis of these SAP were studied in cultured human skin fibroblasts. Using specific antibodies to immunoprecipitate the SAP and to detect the immuno-reactive bands after electrophoresis, some interesting features of these proteins were obtained. These may help us to understand how these proteins regulate sphingolipid metabolism.

Keywords

Gauche Disease Lysosomal Storage Disease Metachromatic Leukodystrophy High Molecular Weight Species High Molecular Weight Form 
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

  • David A. Wenger
    • 1
  • Shinsuke Fujibayashi
    • 1
  1. 1.Department of PediatricsUniversity of Colorado Health Sciences CenterDenverUSA

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