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Molecular Heterogeneity in O-Variant GM2 Gangliosidosis

  • Brian F. O’Dowd
  • Maris H. Klavins
  • Huntington F. Willard
  • Roy Gravel
  • J. Alexander Lowden
  • Don J. Mahuran
Part of the NATO ASI Series book series (NSSA, volume 116)

Abstract

The hydrolysis of GM2-ganglioside by β-hexosaminidase A (Hex A) is unique in its requirement for the proper synthesis and posttranslational processing of three different gene products. Two of these code for the pre-α and β polypeptides that combine to produce active pre-Hex A. The third is a specific Hex A activator protein required to complex with the natural substrate, GM2-ganglioside. Synthesis of mature Hex A and Hex B, the other major Hex isozyme in normal cells composed of only β-subunits, requires processing through the ER and Golgi apparatus with final sequestering in the lysosome. As a result of proteolytic processing in the lysosome the structures of the mature forms of Hex A and Hex B are α(βaβb) and 2(βaβb), where the pre-β chain is proteolytically split into covalently bound nonidentical βa and βb segments.

Keywords

Deletion Line Mutant Cell Line Sandhoff Disease Juvenile Patient Infantile Type 
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

  • Brian F. O’Dowd
    • 1
    • 2
  • Maris H. Klavins
    • 1
    • 2
  • Huntington F. Willard
    • 1
    • 3
  • Roy Gravel
    • 1
    • 3
  • J. Alexander Lowden
    • 1
    • 2
  • Don J. Mahuran
    • 1
    • 2
  1. 1.Research InstituteThe Hospital for Sick ChildrenTorontoCanada
  2. 2.Clinical Biochemistry DepartmentUniversity of TorontoCanada
  3. 3.Department of Medical GeneticsUniversity of TorontoCanada

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