Relative Propensities of Cytochrome c Oxidase and Cobalt Corrins for Reaction with Cyanide and Oxygen: Implications for Amelioration of Cyanide Toxicity.
Relative Propensities of Cytochrome c Oxidase and Cobalt Corrins for Reaction with Cyanide and Oxygen: Implications for Amelioration of Cyanide Toxicity.
复制标题
细胞色素 c 氧化酶和钴 Corrin 与氰化物和氧气反应的相对倾向：对改善氰化物毒性的影响。
DOI：
10.1021/acs.chemrestox.7b00275
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发表时间：
2017
影响因子：
4.1
通讯作者：
Peterson,Jim
中科院分区：
文献类型：
--
作者：
Yuan,Quan;Pearce,LindaL;Peterson,Jim
在中性水溶液中，每个钴氨酰胺与两个氰化物分子的结合可用两个形成常数Kf 1 = 1.1（±0.6）× 105 M ~（-1）和Kf 2 = 8.5（±0.1）× 104 M ~（-1）来描述，即总的氰化物结合常数为1.01 × 10 ~（10）M ~（-2）。与之相比，钴胺素和完全氧化型细胞色素氧化酶的氰化物结合常数分别为7.9（±0.5）× 104 M ~（-1）和1.6（±0.2）× 107 M ~（-1）。用停流分光光度法研究了在中性pH值条件下可宾酰胺与氰化物的结合行为，发现可宾酰胺与氰化物的结合存在两个动力学阶段，即快速阶段和慢速阶段，表观二级速率常数分别为3.2（±0.5）× 103 M ~（-1）s ~（-1）和45（±1）M ~（-1）s ~（-1）。在相同条件下，钴胺素呈现单一的缓慢氰化物结合动力学相，二级速率常数为35（±1）M-1 s-1。所有这三个过程都明显慢于酶周转期间氰化物与络合物IV结合的速率（> 106 M-1 s-1）。总的来说，从这些发现可以理解为什么钴氨酰胺是一种比钴胺素更好的氰化物清除剂，但目前还不清楚钴咕啉如何对氰化物中毒解毒，因为两种化合物本身似乎都不能与细胞色素氧化酶竞争可用的氰化物。此外，在头对头比较试验中也可以明确地表明，该酶确实比钴胺素和钴氨酰胺对氰化物具有更大的亲和力。一个似是而非的解决方案的悖论，钴胺素和cobinamide显然是解毒剂对氰化物中毒，涉及内源性辅助剂一氧化氮，建议。此外，证明了钴咕啉对氧的催化消耗，并且在钴氨酰胺的情况下，当存在细胞色素时，参与其中。特别是在考宾酰胺的情况下，这些氧依赖性反应可能导致对氰化物清除剂恢复氰化物抑制的细胞色素氧化酶活性的能力的错误评估。
In aqueous media at neutral pH, the binding of two cyanide molecules per cobinamide can be described by two formation constants,Kf1= 1.1 (±0.6) × 105M–1andKf2= 8.5 (±0.1) × 104M–1, or an overall cyanide binding constant of ∼1 × 1010M–2. In comparison, the cyanide binding constants for cobalamin and a fully oxidized form of cytochromecoxidase, each binding a single cyanide anion, were found to be 7.9 (±0.5) × 104M–1and 1.6 (±0.2) × 107M–1, respectively. An examination of the cyanide-binding properties of cobinamide at neutral pH by stopped-flow spectrophotometry revealed two kinetic phases, rapid and slow, with apparent second-order rate constants of 3.2 (±0.5) × 103M–1s–1and 45 (±1) M–1s–1, respectively. Under the same conditions, cobalamin exhibited a single slow cyanide-binding kinetic phase with a second-order rate constant of 35 (±1) M–1s–1. All three of these processes are significantly slower than the rate at which cyanide is bound by complex IV during enzyme turnover (>106M–1s–1). Overall, it can be understood from these findings why cobinamide is a measurably better cyanide scavenger than cobalamin, but it is unclear how either cobalt corrin can be antidotal toward cyanide intoxication as neither compound, by itself, appears able to out-compete cytochromecoxidase for available cyanide. Furthermore, it has also been possible to unequivocally show in head-to-head comparison assays that the enzyme does indeed have greater affinity for cyanide than both cobalamin and cobinamide. A plausible resolution of the paradox that both cobalamin and cobinamide clearly are antidotal toward cyanide intoxication, involving the endogenous auxiliary agent nitric oxide, is suggested. Additionally, the catalytic consumption of oxygen by the cobalt corrins is demonstrated and, in the case of cobinamide, the involvement of cytochromecwhen present. Particularly in the case of cobinamide, these oxygen-dependent reactions could potentially lead to erroneous assessment of the ability of the cyanide scavenger to restore the activity of cyanide-inhibited cytochromecoxidase.