Using a functional enzyme model to understand the chemistry behind hydrogen sulfide induced hibernation
Using a functional enzyme model to understand the chemistry behind hydrogen sulfide induced hibernation
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DOI：
10.1073/pnas.0904082106
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发表时间：
2009-12-29
影响因子：
11.1
通讯作者：
Decreau, Richard A.
中科院分区：
文献类型：
--
作者：
Collman, James P.;Ghosh, Somdatta;Decreau, Richard A.
有毒气体H2S是由体内的酶产生的。在中等浓度下，H_2S引起类似冬眠的生理效应。在这里，我们描述的实验，这意味着这种现象可能是由于可逆的抑制酶细胞色素c氧化酶（CCO），减少呼吸过程中的氧气。CcO中氧还原位点的功能模型被用来探索H2S在呼吸过程中的影响。光谱分析表明，该模型结合两个分子的H2S。氧的电催化还原被类似于诱导冬眠的H2S浓度可逆地抑制。这种现象源于H2S与Fe-II卟啉的弱可逆结合，其模拟CcO活性位点中的血红素a（3）。在较低的H2S浓度下未检测到CcO的抑制。然而，在较低浓度下，H2S可能对CcO产生其他生物学效应。例如，H2S迅速还原Fe-III和Cu-II，在氧化形式的功能模型和CcO本身。H2S还还原CcO的生物还原剂细胞色素c，细胞色素c通常从食物代谢中获得其还原当量。因此，据推测，H2S也可能在食物供应不足的冬眠期间作为电子源。
The toxic gas H2S is produced by enzymes in the body. At moderate concentrations, H2S elicits physiological effects similar to hibernation. Herein, we describe experiments that imply that the phenomenon probably results from reversible inhibition of the enzyme cytochrome c oxidase (CcO), which reduces oxygen during respiration. A functional model of the oxygen-reducing site in CcO was used to explore the effects of H2S during respiration. Spectroscopic analyses showed that the model binds two molecules of H2S. The electro-catalytic reduction of oxygen is reversibly inhibited by H2S concentrations similar to those that induce hibernation. This phenomenon derives from a weak, reversible binding of H2S to the Fe-II porphyrin, which mimics heme a(3) in CcO's active site. No inhibition of CcO is detected at lower H2S concentrations. Nevertheless, at lower concentrations, H2S could have other biological effects on CcO. For example, H2S rapidly reduces Fe-III and Cu-II in both the oxidized form of this functional model and in CcO itself. H2S also reduces CcO's biological reductant, cytochrome c, which normally derives its reducing equivalents from food metabolism. Consequently, it is speculated that H2S might also serve as a source of electrons during periods of hibernation when food supplies are low.