Exploring the formation of deleterious heme compounds with sulfide species

PALERMO, JUAN CRUZ; CÓRDOVA, JONATHAN ALEXIS; BARI, SARA ELIZABETH

Córdoba Capital

Congreso; LI Reunión Anual de la Sociedad Argentina de Biofisica; 2023

Sociedad Argentina de Biofisica

The reactivity of heme proteins (HPs) towards reactive sulfur species is of increasinginterest from both biochemical and physiological points of view. The processes understudy include the coordination and reduction of the metal center of metmyoglobin (mMb)and HP model compounds, and the undesired addition of a sulfur atom to the porphyrinring forming green species known as sulfhemes, which has been a drawback duringkinetic studies.These species have been recognized during meat decomposition since theearly 20th century.1Mechanistic proposals on their formation point to the participation of vinyl substituents ofthe type b heme present in the active sites.2 In order to control the formation ofsulfhemes, we reconstituted apomyoglobin with mesohemin IX, a model heme where vinylgroups are substituted by ethyl groups, forming meso-metmyoglobin (meso-mMb). Wecomparatively studied the reactivity of this meso-mMb and mMb, towards 1) consecutiveaddition of H2O2 and Na2S (sulfheme preparation).3 and 2) Na2S or Na2S2 under argon orair atmospheres, to evaluate sulfheme formation, aiming to a HP with restricted formationof sulfheme species for mechanistic studies.We observed that meso-mMb yields a green compound after the addition of H2O2 andNa2S, spectroscopically similar to the sulfMb analog, indicating the putative formation ofsulfmeso-Mb, regardless the absence of vinyl substituents. Also, both proteins undergosulfheme formation by addition of Na2S or Na2S2 in the presence of oxygen. The formationwas more significant for Na2S2 than for Na2S, and faster for mMb. Interestingly, mesometMb is less prone to form sulfheme and may prove helpful as a metMb model for kineticstudies. The results may shed light on the discussion about possible sulfheme formationmechanisms.