Formation of nitric oxide from nitroxyl anion: role of quinones and ferricytochrome c

1 Our previous finding that copper ions oxidize nitroxyl anion released fro m Angeli's salt to nitric oxide prompted us to examine if copper-containing enzymes shared this property. 2 The copper-containing enzyme, tyrosinase, which catalyses the hydroxylati on of monophenols to diphenols and the subsequent oxidation of these to the respective unstable quinone, failed to generate nitric oxide from Angeli's salt by itself, but did so in the presence of tyrosine. 3 L-DOPA, the initial product of the reaction of tyrosinase with tyrosine, was not the active species, since it failed to generate nitric oxide from A ngeli's salt. Nevertheless, L-DOPA and two other substrates, namely, catech ol and tyramine did produce nitric oxide from Angeli's salt in the presence of tyrosinase, suggesting involvement of the respective unstable quinones. In support, we found that 1,4-benzoquinone produced a powerful nitric oxid e signal from Angeli's salt. 4 Coenzyme Q(o), an analogue of ubiquinone, failed to generate nitric oxide from Angeli's salt by itself, but produced a powerful signal in the presen ce of its mitochondrial complex III cofactor, ferricytochrome c. 5 Experiments conducted on rat aortic rings with the mitochondrial complex III inhibitor, myxothiazol, to determine if this pathway was responsible fo r the vascular conversion of nitroxyl to nitric oxide were equivocal: relax ation to Angeli's salt was inhibited but so too was that to unrelated relax ants. 6 Thus, certain quinones oxidize nitroxyl to nitric oxide. Further work is required to determine if endogenous quinones contribute to the relaxant act ions of nitroxyl donors such as Angeli's salt.