Sulfide-mediated reduction of metmyoglobin

PALERMO, JUAN CRUZ; CARLLINNI COLOMBO, MELISA; BOUBETA, FERNANDO MARTÍN; ESTRIN, DARÍO ARIEL; BARI, SARA ELIZABETH

San Luis

Congreso; Encuentro anual de la Sociedad Argentina de Biofísica; 2020

Sociedad Argentina de Biofísica

Along with nitric oxide and carbon monoxide, hydrogen sulfide (H2S) is part of the family of gasotransmitters, that gathers small gaseous molecules, endogenous, with a regulated biosynthesis, and relevant physiological functions after reaching specific targets. While excess quantities of the gasotransmitters are known to be toxic, their physiological functions are exerted at low concentrations. For H2S a physiological participation in cardioprotection, neuroprotection, regulation of blood vessel diameter, and even the induction of hybernation states have been reported.1 As biochemical targets, the thiols of proteins, small thiol compounds (cysteine, glutathione) and the heme iron of hemeproteins have been recognized.2 Our research is focused in the description of the interaction of H2S or its conjugated base hydrosulfide, HS- (pKa1= 6,98 at 25°C)2 with the heme iron of heme compounds. We have evaluated the minimum structural requirements for inorganic sulfide coordination to ferric heme using heme model compounds,3 and aspects of the migration and binding of inorganic sulfide to hemeproteins.4 We observed that the coordination of sulfur species to ferric hemeproteins can subsequently trigger a one-electron reduction, to yield the corresponding ferrous form, with varying reduction rates and with the concomitant formation of colloidal sulfur. In this presentation, we included our ongoing work to elucidate the reduction mechanism of ferric hemeproteins, particularly metmyoglobin, by inorganic sulfide species under biorelevant conditions. Metmyoglobin is reduced by inorganic sulfide by a complex autocatalytical mechanism. It gives the reduction from the MbFeIII(SH-) complex and can be stopped with PBN as a radical scavenger.The induction period shows a monoexponential behavior, which is consistent with the proposal and literature. 6The simulation of both mechanistic proposals are in good agreement with experimental data.EPR studies of the radical species are about to be performed.Final products of the reduction in the presence of scavengers are under study.