Mechanisms of nitrite bioactivation.
Mechanisms of nitrite bioactivation.
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DOI：
10.1016/j.niox.2013.11.002
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发表时间：
2014-04-30
期刊：
影响因子：
--
通讯作者：
Gladwin MT
中科院分区：
文献类型：
--
作者：
Kim-Shapiro DB;Gladwin MT
阴离子亚硝酸盐，曾经被认为是一氧化氮（NO）的惰性氧化产物，现在被认为有助于缺氧血管扩张，生理血压控制和氧化还原信号传导。因此，它在治疗学中的应用正在积极地在临床前模型和人体I-II期临床试验中进行测试。亚硝酸盐生物活化的主要途径包括血红蛋白或钼酸盐蛋白家族成员将其还原为NO，或催化比例失调。这些转化优先发生在缺氧和酸性条件下。许多酶系统将亚硝酸盐还原为NO，它们的活性和重要性由氧张力、特定器官系统和变构和氧化还原效应决定。在这项工作中，我们回顾了不同的亚硝酸盐生物活化机制，重点分析了在不同条件下每种机制的动力学和实验证据的相关性。
It is now accepted that the anion nitrite, once considered an inert oxidation product of nitric oxide (NO), contributes to hypoxic vasodilation, physiological blood pressure control, and redox signaling. As such, its application in therapeutics is being actively testing in pre-clinical models and in human phase I–II clinical trials. Major pathways for nitrite bioactivation involve its reduction to NO by members of the hemoglobin or molybdopterin family of proteins, or catalyzed dysproportionation. These conversions occur preferentially under hypoxic and acidic conditions. A number of enzymatic systems reduce nitrite to NO and their activity and importance are defined by oxygen tension, specific organ system and allosteric and redox effectors. In this work, we review different proposed mechanisms of nitrite bioactivation, focusing on analysis of kinetics and experimental evidence for the relevance of each mechanism under different conditions.
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