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| Author(s): |
Marcelo Gialluisi Bonini
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Conjunto das Químicas (IQ e FCF) (CQ/DBDCQ) |
| Defense date: | 2004-02-27 |
| Examining board members: |
Ohara Augusto;
Ana Campa;
Rafael Radi Isola;
Alicia Juliana Kowaltowski;
Rogerio Meneghini
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| Advisor: | Ohara Augusto |
| Abstract | |
Peroxynitrite (ONOO- + ONOOR), which is formed by the diffusion-controlled reaction between nitric oxide and superoxide anion, has been receiving increasing attention as a mediator of the deleterious effects associated with an overproduction of nitric oxide. Peroxynitrite is a strong oxidant that is able to oxidize and nitrate a variety of biotargets by mechanisms that this work has contributed to establish. Particularly relevant, was the unequivocal demonstration by rapid flow EPR that the rapid reaction between peroxynitrite and the biologically ubiquitous carbon dioxide produces nitrogen dioxide and carbonate radical anion in yields of around 35%. This led us to suggest that in most biological environments peroxynitrite would act through its derived radicals that would oxidize biomolecules to radicals. This hypothesis was clearly supported by our studies of biothioI (cysteine, glutathioneand BSA-cys34) oxidation by peroxynitrite and peroxynitrite/carbon dioxide. In addition, we demonstrated that the reaction between the nitroxide tempol and peroxynitrite-derived radicals is an important step of the mechanism by which tempol diverts peroxynitrite reactivity from nitration to nitrosation of biomolecules. Finally, we demonstrated that there are other potential sources of nitrogen dioxide and carbonate radical anion such as the peroxidase activity of the enzyme Cu,Zn-superoxide dismutase and the enzyme xanthine oxidase turnover. (AU) | |