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
    Fall 2011
  • Type of Item
  • Degree
    Master of Science
  • DOI
  • License
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