Revisit of the Interactions between Hydrogen Sulfide and Heme Proteins

Important roles for hydrogen sulfide (H2S) in physiological and pathological function are emerging. H2S is the fourth signaling gas molecule, following O2, NO and CO, that has been shown to be important for intra- and intermolecular signal transduction. These gas molecules should bind to the heme iron complex and regulate numerous important physiological functions such as transcription, guanylate cyclase, and phosphodiesterase. However, involvement of heme proteins in H2S-regulated functions has not been critically considered. This paper is to sort out the complicated interactions of H2S with heme proteins and to help advance our understanding of the molecular mechanism of the interaction between H2S and heme proteins. Importantly, H2S interacts with the heme iron complex of myoglobin and hemoglobin in the presence of H2O2, forming sulfheme (sulfur-incorporated porphyrin) iron complex with markedly different physicochemical characters (such as oxygen binding affinity) in contrast to those of the normal heme iron complex. It is suggested that involvement of the heme proteins in H2S-regulated physiological and pathological functions, in particular under oxidative stress conditions, is much more crucial than generally thought.