Reactions of Ferrous Coproheme Decarboxylase (HemQ) with O 2 and H 2 O 2 Yield Ferric Heme b.

A recently discovered pathway for the biosynthesis of heme b ends in an unusual reaction catalyzed by coproheme decarboxylase (HemQ), where the Fe(II)-containing coproheme acts as both substrate and cofactor. Because both O ₂ and H ₂ O ₂ are available as cellular oxidants, pathways for the reaction involving either can be proposed. Analysis of reaction kinetics and products showed that, under aerobic conditions, the ferrous coproheme-decarboxylase complex is rapidly and selectively oxidized by O ₂ to the ferric state. The subsequent second-order reaction between the ferric complex and H ₂ O ₂ is slow, pH-dependent, and further decelerated by D ₂ O ₂ (average kinetic isotope effect of 2.2). The observation of rapid reactivity with peracetic acid suggested the possible involvement of Compound I (ferryl porphyrin cation radical), consistent with coproheme and harderoheme reduction potentials in the range of heme proteins that heterolytically cleave H ₂ O ₂ . Resonance Raman spectroscopy nonetheless indicated a remarkably weak Fe-His interaction; how the active site structure may support heterolytic H ₂ O ₂ cleavage is therefore unclear. From a cellular perspective, the use of H ₂ O ₂ as an oxidant in a catalase-positive organism is intriguing, as is the unusual generation of heme b in the Fe(III) rather than Fe(II) state as the end product of heme synthesis.