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Revisiting the antifibrinolytic effect of carboxypeptidase N: novel structure and regulation

  • Author / Creator
    Swanson, Pascale Libront
  • Carboxypeptidase N (CPN) is a plasma carboxypeptidase that was discovered in the 1960s as a regulator of inflammation and vascular tone. Through the removal of carboxy-terminal basic residues, CPN alters the activity or binding specificity of inflammatory mediators and vasoactive peptides. CPN shares significant homology with carboxypeptidases known to mediate antifibrinolysis through the removal of basic residues from fibrin clots, which would otherwise stimulate fibrinolysis. Despite the similarity of these enzymes, CPN is generally regarded as lacking a role in fibrinolysis. This thesis demonstrates that CPN is indeed a capable antifibrinolytic enzyme, and that the antifibrinolytic activity of CPN was previously undisclosed due to the presence of a circulating CPN inhibitor, which is likely the free CPN2 subunit. This inhibitor is described for the first time here. Furthermore, potential mechanisms of inhibition and mechanisms of enhancing activity of CPN are proposed based upon the additional structural characterization of CPN presented here.

  • Subjects / Keywords
  • Graduation date
    2010-11
  • Type of Item
    Thesis
  • Degree
    Master of Science
  • DOI
    https://doi.org/10.7939/R3TG9J
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.
  • Language
    English
  • Institution
    University of Alberta
  • Degree level
    Master's
  • Department
    • Medical Sciences - Pediatrics
  • Supervisor / co-supervisor and their department(s)
    • Bajzar, Laszlo (Pediatrics)
    • Schulz, Richard (Pediatrics)
  • Examining committee members and their departments
    • Michalak, Marek (Biochemistry)