This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Typically peroxynitrite (PN) inactivates thiolate-ligated hemes proteins through tyrosine nitration. These nitrated proteins are detected and thought to play a role in diseases such as Parkinson?s and Alzheimer?s. They also have been shown to have a significant presence in neurodegenerative and cardiovascular disorders. Ullrich and coworkers reported that the reaction of PN with P450?s yielded P450 compound II (an Fe(IV)hydroxide species, similar to the rebound intermediate of cytochrome P450). The ?P450-II? thus formed was unusual in that it was relatively stable and could be produced in high yield. The yield and stability of the P450-PN intermediate are in stark contrast to the results obtained when P450-II is generated with more traditional oxidants (e.g. peracetic acid or meta-chloroperbenzoic acid).
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