Send to

Choose Destination
Nitric Oxide. 1999;3(2):142-52.

Peroxynitrite reaction with heme proteins.

Author information

Faculty of Biology, University of Konstanz, Germany.


We have reported that low levels of peroxynitrite (PN) can cause inactivation of the heme-thiolate protein prostacyclin (PGI2)-synthase by nitration of a tyrosine residue. To prove that iron catalysis is involved we studied the interaction of PN with microperoxidase and P450nor, a heme-thiolate protein of known structure. Spectral and kinetic analyses allow to conclude on a ferryl nitrogen dioxide complex as an intermediate which decomposes in the presence of an excess of PN under formation of dioxygen, nitrite, and nitrate. This occurs in a catalytic cycle which was more efficient with P450nor than with microperoxidase. If phenol was added to the reaction mixtures of PN and the ferric complexes the ratio of hydroxylated to nitrated phenols decreased compared to the metal-free system. Phenol competed with the formation of dioxygen indicating that the ferryl intermediate was involved in both pathways. One therefore can postulate that the ferryl complex reacts with phenol to give the phenoxyradical which is nitrated in the presence of nitrogen dioxide but does not give hydroxylated products as with metal-free PN. Alternately, the ferryl nitrogen dioxide complex can oxidize a second PN molecule to the radical, *OONO, which can decompose to dioxygen and NO. The latter forms N2O3, with the remaining *NO2 radical. A third pathway consists in the isomerization to nitrate which also is catalyzed by the heme proteins since the ratio of nitrite/nitrate does not change significantly during the catalytic reaction with excess of PN. Our data explain the mechanism of nitration of PGI2-synthase, suggest a role of P450nor as a PN scavenger, and favor heme-thiolate complexes for trapping PN.

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center