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4-aminobenzoic acid hydrazide mediated inhibition of Microperoxidase-11: catalytic inhibition by reactive metabolites.

  • Author / Creator
    Arvadia, Pratik
  • Currently, there is lack of clinical therapeutics for inhibiting myeloperoxidase mediated pathogenesis. We used 4-aminobenzoic acid hydrazide (4-ABAH), the most potent irreversible inhibitor of myeloperoxidase and microperoxidase-11 to obtain mechanistic insight on the role of reactive metabolites in catalytic inhibition. We investigated heme spectrum and peroxidase activity of MP-11 in the presence of 4-ABAH. Significant inhibition of MP-11 by 4-ABAH was observed. We performed ESR spin trapping studies on 4-ABAH reactive metabolites using 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) and detected carbon-centered radicals. We performed MALDI and determined the change in elemental composition that occurred in these reactions. These masses were assigned to free radical metabolites of 4-ABAH and were not observed in reactions containing DMPO. We successfully determined MP-11 immunoreactivity using western blotting. We conclude that the 4-ABAH free radical metabolites bound to MP-11 were involved in the catalytic inhibition.

  • Subjects / Keywords
  • Graduation date
    2011-11
  • Type of Item
    Thesis
  • Degree
    Master of Science
  • DOI
    https://doi.org/10.7939/R3M35C
  • 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
    • Faculty of Pharmacy and Pharmaceutical Sciences
  • Supervisor / co-supervisor and their department(s)
    • Siraki, Arno (Pharmaceutical Sciences)
  • Examining committee members and their departments
    • Acker, Jason (Laboratory Medicine and Pathology)
    • Seubert, John (Pharmaceutical Sciences)