SCHEME 1.
Proposed reaction mechanisms for the reaction of T. cruzi Fe-SODs with peroxynitrite. Peroxynitrite anion (ONOO−, 80% at pH 7.4) reacts with the FeIII atom of the Fe-SODs, yielding the corresponding oxo-metal complex (SOD-FeIV=O) with •NO2 generation (reaction I). SOD-FeIV=O oxidizes the active site Tyr (Tyr35 in Fe-SODB and Tyr36 in Fe-SODA) to its corresponding tyrosyl radical (SOD-FeIII···Tyr35-O•) (reaction II). SOD-FeIII···Tyr35-O• rapidly combines with •NO2 (I), yielding the nitrated and inactivated enzyme SOD-FeIII···Tyr35-NO2 (reaction III). In T. cruzi Fe-SODB (reaction IV), Cys83-S− repairs FeIII···Tyr35-O•, regenerating FeIII···Tyr35-OH through an IET process. The homolytic cleavage of ONOOH (reaction V) and the nucleophilic addition of ONOO− to CO2 (reaction VI) (reviewed in Ref. 89) compete with reaction I and decrease the extents of Tyr35 nitration and enzyme inactivation.