Heme Iron as Target for Inorganic Sulfide

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

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

Heme Iron as Target for HydrodisulfideJuan Cruz Palermo,a,b Melisa Carllinni Colombo, Fernando Boubeta,a Darío Estrin,a,b Sara Bari aa Universidad de Buenos Aires. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Química Física de los Materiales, Medio Ambiente y Energía (INQUIMAE). Facultad de Ciencias Exactas y Naturales, Buenos Aires, Argentina. b Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Inorgánica, Analítica y Química Física. Buenos Aires, Argentina. juancpalermo@gmail.com; sara.elizabeth.bari@gmail.comHydrogen 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.1,2 H2Sn (n=2,3) have been demonstrated to be products of the H2S forming enzyme, the 3-mercaptopyruvate sulfurtransferase.1,3 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.4,5 We present herein a study of the kinetics of the interaction of disodium disulfane, Na2S2,6 with metmyoglobin (FeIIIMb) at neutral pH, and a comparison with the results previously reported using Na2S.7We 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¯),4,7 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.References(1) Kimura, Y.; Toyofuku, Y.; Koike, S.; Shibuya, N.; Nagahara, N.; Lefer, D.; Ogasawara, Y.; Kimura, H. Scientific Reports 2015, 5 (1).(2) Nagahara, N.; Koike, S.; Nirasawa, T.; Kimura, H.; Ogasawara, Y. Biochemical and Biophysical Research Communications 2018, 496 (2), 648.(3) Koike, S.; Kawamura, K.; Kimura, Y.; Shibuya, N.; Kimura, H.; Ogasawara, Y. Free Radical Biology and Medicine 2017, 113, 355.(4) Bostelaar, T.; Vitvitsky, V.; Kumutima, J.; Lewis, B. E.; Yadav, P. K.; Brunold, T. C.; Filipovic, M.; Lehnert, N.; Stemmler, T. L.; Banerjee, R. Journal of the American Chemical Society 2016, 138 (27), 8476.(5) Galardon, E.; Huguet, F.; Herrero, C.; Ricoux, R.; Artaud, I.; Padovani, D. Dalton Transactions 2017, 46 (24), 7939.(6) Gao, Y.; Toubaei, A.; Kong, X.; Wu, G. Chemistry - A European Journal 2015, 21 (48), 17172.(7) Boubeta, F. M.; Bieza, S. A.; Bringas, M.; Estrin, D. A.; Boechi, L.; Bari, S. E. Inorganic Chemistry 2018, 57 (13), 7591.(8) Jensen, B.; Fago, A. Journal of Inorganic Biochemistry 2018, 182, 133.(9) Koppenol, W. H.; Bounds, P. L. Archives of Biochemistry and Bio