Degradation Studies on Plasma Prealbumin

  • Martha Skinner
  • Lawreen H. Connors
  • Herbert M. Kagan
  • Phillip Stone
  • Alan S. Cohen


The variant molecular forms of prealbumin (transthyretin, TTR) protein are necessary for the formation of amyloid fibrils in individuals with the hereditary (AF) type of amyloid disease. It is also possible that a proteolytic change in the prealbumin occurs before fibril deposition. This is suggested by the finding of multiple prealbumin fragments of various sizes in two reports and the N-terminal deletions of one, two or three amino acids in others.

We examined the proteolysis of prealbumin isolated from the plasma of patients with AF amyloidosis known to be of the met/val 30 variant type and from normal individuals. The isolated proteins were reacted with human neutrophil elastase, trypsin, chymotrypsin, papain, S. aureus protease V8, pepsin, pronase, subtilisin and thermolysin. Results of proteolysis were examined by polyacrylamide gel electrophoresis, amino-terminus analysis and circular dichroism analysis.

After digestion with human neutrophil elastase significant perturbation of the beta-sheet conformation of both prealbumin isolated from AF patients as well as normal prealbumin could be shown by circular dichroic analysis. The effect was much more dramatic in the AF prealbumin exceeding that expected due to a 30% content of variant molecules in the protein mixture. This suggests that proteolysis occurs differently in variant prealbumin and may be important in its formation into amyloid fibrils.


Amyloid Fibril Human Neutrophil Elastase Familial Amyloid Polyneuropathy Familial Amyloidotic Polyneuropathy Circular Dichroism Analysis 
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Copyright information

© Springer Science+Business Media New York 1988

Authors and Affiliations

  • Martha Skinner
    • 1
  • Lawreen H. Connors
    • 1
  • Herbert M. Kagan
    • 1
  • Phillip Stone
    • 1
  • Alan S. Cohen
    • 1
  1. 1.Boston University School of MedicineBostonUSA

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