The catabolic fate of nitric oxide - The nitric oxide oxidase and peroxynitrite reductase activities of cytochrome oxidase
The catabolic fate of nitric oxide - The nitric oxide oxidase and peroxynitrite reductase activities of cytochrome oxidase
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DOI：
10.1074/jbc.m109838200
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发表时间：
2002-04-19
影响因子：
4.8
通讯作者：
Peterson, J
中科院分区：
文献类型：
--
作者：
Pearce, LL;Kanai, AJ;Peterson, J
通过对单个细胞的微传感器测量显示，心肌细胞内源性进化一氧化氮的刺激导致瞬时一氧化氮浓度达到几百纳摩尔。在这些亚微摩尔浓度下，没有证据表明所产生的一氧化氮与细胞中存在的氧合肌红蛋白之间会发生预期的反应：一氧化氮+氧合肌红蛋白-硝酸> +氧合肌红蛋白。电子顺磁共振波谱没有检测到肌红蛋白的形成，微传感器测量显示一氧化氮几乎定量地转化为亚硝酸盐而不是硝酸盐离子。此外，亚硝酸盐的形成速度太快，无法用非酶的方法来解释。在细胞色素c氧化酶催化的一系列反应的基础上，可以合理地解释一氧化氮本质上定量和快速分解为亚硝酸盐离子的过程。用纯化的血红蛋白在体外证明，末端氧化酶可以与氧肌红蛋白竞争可用的一氧化氮。在正常的生理和大多数病理（非炎症）条件下，与细胞色素c氧化酶的反应是NO从富含线粒体的细胞中去除的主要途径。
Stimulation of cardiomyocytes to endogenously evolve nitric oxide is shown by microsensor measurements on single cells to lead to transient nitric oxide concentrations of a few hundred nanomolar. At these submicromolar concentrations, no evidence could be found for the expected reaction between nitric oxide generated and the oxymyoglobin present in the cells: nitric oxide + oxymyoglobin --> nitrate + metmyoglobin. No metmyoglobin formation was detected by electron paramagnetic resonance spectroscopy, and microsensor measurements revealed near quantitative conversion of the nitric oxide to nitrite rather than nitrate ion. Moreover, the rate of nitrite formation is shown to be too rapid to be accounted for by non-enzymatic means. The essentially quantitative and rapid catabolism of nitric oxide to nitrite ion can plausibly be explained on the basis of a cycle of reactions catalyzed by cytochrome c oxidase. It is demonstrated with the purified hemoproteins in vitro that the terminal oxidase can outcompete oxymyoglobin for available nitric oxide. It is proposed that under normal physiological and most pathological (non-inflammatory) conditions, reaction with cytochrome c oxidase is the major route by which NO is removed from mitochondria-rich cells.