- 254 views
- 395 downloads
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
- Thesis
-
- Degree
- Master of Science
-
- 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.