Unraveling the Reaction between Heme (FeIV=O) Moiety and H2S

血红蛋白（Hb）和肌红蛋白（Mb）与过氧化氢（H2 O2）发生过氧化反应， 卟啉/r-阳离子自由基铁基化合物I（Fe ′ v =O Por*+）和铁基化合物II（Fe ′ v =O Por）， 对红细胞非常敏感和有害。同时，硫化氢（H2S）进入血液 河流，通过环境暴露或细菌感染，可以与这些物种相互作用，导致 形成硫血红蛋白（sulfHb）和硫肌红蛋白（sulfMb），随后破坏Hb， Mb函数。这些失活的蛋白质，其特定的血红素中间体和反应机制仍然是 未知，其特征在于具有在620 nm处的吸收带的血红素IX二氢卟酚衍生物 区域，带有饱和的4-乙烯基，H2S共价结合在该区域的<$-<$双键上， 吡咯C我们的最新数据表明，在相同的实验条件下，H2 O2和H2S， 来自Lucina pectinata的血红蛋白I、II和III（分别为Hbl和Hbll/Hbll 1）不形成这些血红蛋白。 硫血红素衍生物。Hbl递送H2S，而Hbll和Hblll将O2运输到共生细菌，尽管存在H2S。 在功能和化学结构上的多样性，在L. 栉蛤这种区别不被理解，将被用作理解 由于形成sulfHb 1和sulfHb 11/sulfHb 11应通过 通过与H2 O2和H2S反应产生的相同的高价血红素中间体，根据： H2s [Hbl（Fem）或Hbl（Fe”-O2）] + H2O2~-*（Fe 'v =O Por <$+）+（Felv=O Por）> SulfHbl（A） 化合物I化合物II Hbl和Mb之间的另一个显著差异是铁基化合物I是Mb的近一千倍。 前者比后者更稳定。因此，我们的假设表明，硫血红素蛋白的机制， 形成可能取决于（1）血红素中心周围的氨基酸环境，（2） 铁基物种（化合物I和II）的寿命，以及（3）外围铁基物种的取向和结构。 血红素取代基为了探索这些替代方案，我们将监测648 nm、620 nm和419 nm的波段 通过UV-Vis和停止流动分别测定Hbl化合物I、sulfHbl和化合物II的nm特征， 在血红素蛋白（Mb、Hb 1、Hb 1突变体和Hb 11/Hb 111）的反应（A）后。中间和最后 结构将通过共振拉曼、NMR和X射线光谱学来追踪。数据将允许 评论（i）化合物I和II在人sulfHb和sulfMb形成中的作用，（ii）阐明 H2S的吡咯“C”反应的选择性，和（iii）有助于直接战略的发展 用于治疗和使sulfHb或sulfMb可逆为具有生物活性的人Hb和Mb。

The peroxidative reactions of hemoglobin (Hb) and myoglobin (Mb) with hydrogen peroxide (H2O2) produce porphyrin /r-cation radical ferryl compound I (Fe'v=O Por*+) and ferryl compound II (Felv=O Por), which are very reactive and detrimental to red cells. At the same time, hydrogen sulfide (H2S) entering the blood stream, by environmental exposure or bacterial infections, can interact with these species leading to the formation of sulfhemoglobin (sulfHb) and sulfmyoglobin (sulfMb) with the subsequent disruption of Hb and Mb function. These inactive proteins, whose specific heme intermediates and reaction mechanism are still unknown, are characterized by a protoheme IX chlorin derivative with an absorption band at the 620 nm region, bearing the saturated 4-vinyl group with a H2S covalently bound across the¿-¿ double bond of the pyrrole "C". Our latest data show that under the same experimental conditions, of H202 and H2S, the hemoglobins I, II and III, (Hbl and Hbll/Hblll, respectively), from Lucina pectinata do not form these sulfheme derivatives. Hbl delivers H2S, while Hbll and Hblll transport 02 to symbiotic bacteria, despite the diversity in function and chemical structure no sulfheme-proteins derivatives have been detected in the L pectinata clam. This discrimination is not understood and will be used as a model to comprehend the mechanism toward sulfHb and sulfMb since the formation sulfHbl and sulfHbll/sulfHblll should proceed via the same high valent heme intermediates generated by the reaction with H2O2and H2S according to: H2S [Hbl (Fem) or Hbl (Fe"-O2) ] + H2O2~-* (Fe'v=O Por¿+) + (Felv=O Por) > SulfHbl (A) Compound I Compound II O2 Other notable difference between Hbl and Mb is that the ferryl compound I is near one thousand times more stable in the former than in the latter. Thus, our hypothesis suggests that the mechanism of sulfhemeprotein formation may depends on (1) the amino acid environment surrounding the heme center, (2) the life time of the ferryl species (compound I and II), and (3) the orientation and structure of the peripheral heme substituents. To explore these alternatives, we will monitor the bands at 648 nm, 620 nm, and 419 nm characteristic of Hbl compound I, sulfHbl, and compound II, respectively, by UV-Vis and stopped flow, upon the reaction (A) of hemeproteins (Mb, Hbl, Hbl mutants, and Hbll/Hblll). The intermediate and final structures will be pursued by resonance Raman, NMR and X-ray spectroscopy. The data will allow commenting on (i) the role of compound I and II in the formation of human sulfHb and sulfMb, (ii) unravel the selectivity of H2S for the pyrrole "C" reaction , and (iii) contribute to the development of direct strategies for the treatment and reversibility of sulfHb or sulfMb to the biological active human Hb and Mb.