Heme iron as target for hydrodisulfide

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

Montevideo

Simposio; Thiols, key players in the redox regulation of cellular functions; 2019

International Centre for Genetic Engineering and Biotechnology

Hydrogen polysulfides, H2Sn (n>1), are gaining growing interest because some of the physiological roles formerly attributed to endogenous hydrogen sulfide, H2S, are better described as a consequence of their more potent action. H2Sn (n=2,3) have been demonstrated to be products of the H2S forming enzyme, the 3-mercaptopyruvate sulfurtransferase. The interaction of related low molecular weight persulfide species (RSSnH, n=1) with ferric hemeproteins as potential targets of biochemical interest has been recently explored, and the metal centered reduction or the coordination have been reported as products. We present herein a study of the kinetics of the interaction of disodium disulfane, Na2S2, with metmyoglobin (FeIIIMb) at neutral pH, and a comparison with the results previously reported using Na2S.We observed that FeIIIMb 8 x 10-6 M, in the presence of Na2S2 (R disulfane/ Mb = 10, 20, 30; pH 6.8, anaerobic, 25ºC) completely yielded the reduced hemeprotein, FeIIMb. The intermediacy of a species absorbing at 423, 545, and 578 nm, named P423, different from the previously characterized MbFeIII(SH¯), was observed at 25ºC when ratio was R disulfane/ Mb=10. The intermediate P423 was also detected under stopped flow conditions at 10ºC (pH 6.8, anaerobic, RMb/disulfane= 100), and hence tentatively assigned to the elementary step forming MbFeIII(SSH¯).The reaction of FeIIIMb with excess Na2S2 at 25ºC is characterized by the exponential growth of the well characterized FeIIMb. Comparatively, the Na2S-mediated reduction reaction of FeIIIMb shows an overall significantly slower formation of FeIIMb.8 In average, the rate constant for the reduction reaction of FeIIIMb by Na2S2 is 35% faster than the analogous with Na2S. The results suggest that interaction of disulfanes with MbFeIII might have a role in the heme-mediated oxidative detoxification of sulfides. Also, the fast reduction mediated by Na2S2 suggests a potential function as antioxidant