Blomberg Margareta R A, Siegbahn Per E M
Department of Organic Chemistry, Arrhenius Laboratory, Stockholm University, SE-106 91, Stockholm, Sweden.
Department of Organic Chemistry, Arrhenius Laboratory, Stockholm University, SE-106 91, Stockholm, Sweden.
Biochim Biophys Acta. 2014 Jul;1837(7):1165-77. doi: 10.1016/j.bbabio.2014.01.002. Epub 2014 Jan 11.
Cytochrome c oxidase is a superfamily of membrane bound enzymes catalyzing the exergonic reduction of molecular oxygen to water, producing an electrochemical gradient across the membrane. The gradient is formed both by the electrogenic chemistry, taking electrons and protons from opposite sides of the membrane, and by proton pumping across the entire membrane. In the most efficient subfamily, the A-family of oxidases, one proton is pumped in each reduction step, which is surprising considering the fact that two of the reduction steps most likely are only weakly exergonic. Based on a combination of quantum chemical calculations and experimental information, it is here shown that from both a thermodynamic and a kinetic point of view, it should be possible to pump one proton per electron also with such an uneven distribution of the free energy release over the reduction steps, at least up to half the maximum gradient. A previously suggested pumping mechanism is developed further to suggest a reason for the use of two proton transfer channels in the A-family. Since the rate of proton transfer to the binuclear center through the D-channel is redox dependent, it might become too slow for the steps with low exergonicity. Therefore, a second channel, the K-channel, where the rate is redox-independent is needed. A redox-dependent leakage possibility is also suggested, which might be important for efficient energy conservation at a high gradient. A mechanism for the variation in proton pumping stoichiometry over the different subfamilies of cytochrome oxidase is also suggested. This article is part of a Special Issue entitled: 18th European Bioenergetic Conference.
细胞色素c氧化酶是一类膜结合酶的超家族，催化分子氧向水的放能还原反应，在膜上产生电化学梯度。该梯度的形成既源于电生化学过程，即从膜的两侧获取电子和质子，也源于质子跨膜泵出。在最有效的亚家族，即氧化酶的A家族中，每一步还原反应都会泵出一个质子，考虑到其中两个还原步骤很可能只是微弱放能这一事实，这一现象令人惊讶。基于量子化学计算和实验信息的结合，本文表明，从热力学和动力学角度来看，即使在还原步骤中自由能释放分布不均的情况下，每一个电子也应该有可能泵出一个质子，至少达到最大梯度的一半。在此进一步发展了一种先前提出的泵浦机制，以解释A家族中使用两个质子转移通道的原因。由于通过D通道向双核中心转移质子的速率依赖于氧化还原状态，对于放能较低的步骤来说可能会变得过慢。因此，需要第二个通道，即K通道，其速率不依赖于氧化还原状态。本文还提出了一种依赖于氧化还原状态的泄漏可能性，这对于在高梯度下高效的能量守恒可能很重要。本文还提出了一种细胞色素氧化酶不同亚家族之间质子泵浦化学计量变化的机制。本文是名为“第18届欧洲生物能量学会议”的特刊的一部分。
