Antagonism of nitric oxide toward the inhibition of cytochrome c oxidase by carbon monoxide and cyanide.
Antagonism of nitric oxide toward the inhibition of cytochrome c oxidase by carbon monoxide and cyanide.
复制标题
一氧化氮对一氧化碳和氰化物对细胞色素c氧化酶的抑制有拮抗作用。
DOI：
10.1021/tx800140y
复制
发表时间：
2008
影响因子：
4.1
通讯作者：
Peterson,Jim
中科院分区：
文献类型：
--
作者：
Pearce,LindaL;LopezManzano,Elisenda;Martinez-Bosch,Sandra;Peterson,Jim
呼吸抑制剂CO、CN-和NO在执行其急性毒性作用时作用的主要线粒体靶点是电子传递链的复合物IV，细胞色素氧化酶。然而，文献中关于此类毒物的协同作用的研究很少。因此，CO + CN-、NO + CN-和NO + CO对细胞色素氧化酶制剂活性的联合抑制作用也被报道。只有在CO + CN−的情况下，两种抑制剂的作用才像预期的那样是相加的。NO似乎对其他两种抑制剂的作用具有拮抗作用;也就是说，CO和CN-对酶活性的影响在NO存在时得到改善。为了进一步阐明这些观察结果，还简要研究了细胞色素氧化酶和血红蛋白中血红素结合的CN−被NO取代的配体。这些结果表明，NO从铁血红素蛋白中置换CN−的速率受到血红素还原的限制，而在酶的情况下，非配体结合电子转移中心的存在促进了反应。研究结果进行了讨论的想法，NO不作为一个经典的可逆（解离）抑制剂。
The principle mitochondrial target where the respiratory inhibitors CO, CN−, and NO act in the execution of their acute toxic effects is complex IV of the electron-transport chain, cytochromecoxidase. However, there is a paucity of studies in the literature regarding the concerted effects of such poisons. Accordingly, the combined inhibitory effects of CO + CN−, NO + CN−, and NO + CO on the activity of cytochromecoxidase preparations are reported. Only in the case of CO + CN−do the effects of the two inhibitors seem to be additive as expected. NO appears to be antagonistic toward the effects of the other two inhibitors; that is, the effects of both CO an CN−on enzyme activity are ameliorated by NO when present. To further clarify these observations, the ligand substitutions of heme-bound CN−by NO in cytochromecoxidase and hemoglobin have also been briefly investigated. These results suggest that displacement of CN−from the ferric hemoproteins by NO is rate-limited by heme reduction-and in the case of the enzyme, the presence of nonligand-binding electron-transfer centers facilitates the reaction. The findings are discussed in relation to the idea that NO does not behave as a classic reversible (by dissociation) inhibitor.