KINETICS OF NITRIC OXIDE BINDING TO HEMOPROTEINS

血管内给药的无细胞血红蛋白似乎是 与肺和全身血压升高密切相关。 这种高血压反应被归因于 血红蛋白和内皮衍生松弛因子(EDRF)，即 现在被认为是一氧化氮(NO)。我们探索了相互作用 在NO和氧化形式之间的一些化学修饰 血红蛋白。这些血红蛋白是血液替代品，因为 它们较低的氧亲和力和较高的四聚体稳定性 结构。利用快速反应技术，停流装置， 我们有文件证明，在最初的不接受治疗的情况下 与这些蛋白质的铁形式结合，并在随后的NO- 驱动减速步骤。因为NO将氧合血红蛋白氧化成铁血红蛋白 (MetHb)在体内非常迅速，我们假设一个氧化还原循环 NO和metHb之间的相互作用可能是导致 NO作为生物转导因子，导致血管张力改变 对不同的血红蛋白制剂观察到不同的效果。工作是 NO与其他物质相互作用机制的研究进展(S) 充分了解血红素蛋白在多大程度上携带血红素 化学和其他结构特征决定了NO与TO的结合 血球蛋白。在这方面，我们开始研究稳态和 简单和复杂NO反应的暂态动力学 分别是肌红蛋白和过氧化氢酶等血红蛋白。我们也是 硝酸根的产物过亚硝酸根(Oono-)的反应性研究 氧化物与超氧离子的反应，被认为是在 血管壁。这最终将有助于设计 具有理想的氧结合特性的血红蛋白， 表现出被抑制的与NO反应的能力。

Intravascular administration of cell-free hemoglobin appears to be strongly correlated with a rise in pulmonary and systemic blood pressure. This hypertensive response has been attributed to the reaction between hemoglobin and the endothelium-derived relaxing factor (EDRF), which is now believed to be nitric oxide (NO). We explored the interactions between NO and the oxidized forms of a number of chemically modified hemoglobins. These hemoglobins are blood substitute candidates due to their lower oxygen affinity and greater stability of their tetrameric structures. Using fast reaction techniques, the stopped flow apparatus, we documented that there are differences in the rate of the initial NO binding to the ferric forms of these proteins and in the subsequent NO- driven reduction step. Since NO oxidizes oxyhemoglobin to ferrihemoglobin (metHb) extremely rapidly in vivo, we hypothesized that a redox cycle between NO and metHb could be partially responsible for the depletion of NO as a biological transducer, leading to altered vascular tone with variable effects observed for different hemoglobin preparations. Work is in progress to explore the mechanism(s) of interactions of NO with other hemoproteins to fully understand the degree to which heme pocket chemistry and other structural features determine the binding of NO to hemoproteins. In this regard, we began to study both steady state and transient kinetics of NO reactions with simple and more complex hemoproteins such as myoglobin and catalase, respectively. We are also exploring the reactivity of peroxynitrite (OONO-), a product of nitric oxide reaction with superoxide ions, which is thought to be produced in the vascular wall. This will ultimately contribute to the design of hemoglobin that, along with desirable oxygen binding characteristics, exhibits a suppressed ability to react with NO.