Figure 3. Non-redox iron-dependent enzymes are inactivated by hydrogen peroxide and superoxide.

(A) Mononuclear enzymes (here, ribose-5-phosphate 3-epimerase, RPE) employ an active-site divalent metal (Me²⁺) to stabilize anionic reaction intermediates. (B) In the substrate-free enzyme (here, peptide deformylase, PDF), the solvent exposure of the catalytic iron atom leaves it vulnerable to oxidation by H₂O₂ (left branch) and O₂- (right). Dissociation of ferric iron inactivates the enzyme. If cysteine coordinates the metal, the ferryl radical generated by H₂O₂ is quickly quenched, and activity can be restored by reduction of the cysteine sulfenate residue and remetallation. Thioredoxins are likely mediators of the reduction. Some organisms employ manganese or zinc in place of iron, conferring full resistance to ROS.