P90 Hydrogen sulfide activation by hemeproteins: Implications of the sulfheme scenario

Abstract

Hydrogen sulfide (H2S) in the presence of O2 or H2O2, reacts with hemoglobin(Hb) and myoglobin(Mb), to generate specifically a covalent modification of the heme pyrrole ring bearing the4 − vinyl group, to produce sulfmyoglobin and sulfhemoglobin derivatives. These species have lower O2 affinity affecting the heme protein functionality and generating sulfhemoglobinemia. Peroxidases and catalases, with distal heme pocket, similar to Hb and Mb, also produce sulfheme. The reaction has been explored, upon interaction of H2S, RSH species, with O2 and H2O2 and several hemeproteins, using UV–vis, resonance Raman, EPR spectroscopy, and theoretical calculations. The results show that the formation of the sulfheme derivative requires the presence of a: (a) proton donor from the HSR species; (b) HisE7 residue in the heme distal site with an adequate orientation form an active ternary complex; and (c) the intermediate involving the HisE7, the hydro peroxo {HemeFe (III)-OOH}, and H2S species. Homolysis of the moiety generates oxoheme ferryl compound II and HS radical. Since the rate of sulfMb formation decreases with the concentration of hydrosulfide HS− ion, ferryl compound II and the HS species are the predominant intermediates in the reaction of sulfheme formation. The HS attacks the ferryl compound II, producing the final sulfheme derivative. Under this state, H2S avoids the presence of oxoferryl heme species compound I and limits the further generation protein radicals and ROS species. The finding opens a window to further explore H2S as an antioxidant agent and unravels the arena for H2S activation by other proteins.