Crofts Antony R, Lhee Sangmoon, Crofts Stephanie B, Cheng Jerry, Rose Stuart
Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Biochim Biophys Acta. 2006 Aug;1757(8):1019-34. doi: 10.1016/j.bbabio.2006.02.009. Epub 2006 Mar 15.
The Q-cycle mechanism of the bc1 complex explains how the electron transfer from ubihydroquinone (quinol, QH2) to cytochrome (cyt) c (or c2 in bacteria) is coupled to the pumping of protons across the membrane. The efficiency of proton pumping depends on the effectiveness of the bifurcated reaction at the Q(o)-site of the complex. This directs the two electrons from QH2 down two different pathways, one to the high potential chain for delivery to an electron acceptor, and the other across the membrane through a chain containing heme bL and bH to the Qi-site, to provide the vectorial charge transfer contributing to the proton gradient. In this review, we discuss problems associated with the turnover of the bc1 complex that center around rates calculated for the normal forward and reverse reactions, and for bypass (or short-circuit) reactions. Based on rate constants given by distances between redox centers in known structures, these appeared to preclude conventional electron transfer mechanisms involving an intermediate semiquinone (SQ) in the Q(o)-site reaction. However, previous research has strongly suggested that SQ is the reductant for O2 in generation of superoxide at the Q(o)-site, introducing an apparent paradox. A simple gating mechanism, in which an intermediate SQ mobile in the volume of the Q(o)-site is a necessary component, can readily account for the observed data through a coulombic interaction that prevents SQ anion from close approach to heme bL when the latter is reduced. This allows rapid and reversible QH2 oxidation, but prevents rapid bypass reactions. The mechanism is quite natural, and is well supported by experiments in which the role of a key residue, Glu-295, which facilitates proton transfer from the site through a rotational displacement, has been tested by mutation.
bc1复合物的Q循环机制解释了从泛醌（醌醇，QH2）到细胞色素（cyt）c（或细菌中的c2）的电子转移是如何与质子跨膜泵浦相偶联的。质子泵浦的效率取决于复合物Q(o)位点上分支反应的有效性。这将QH2中的两个电子导向两条不同的途径，一个导向高电位链以传递给电子受体，另一个通过包含血红素bL和bH的链跨膜传递到Qi位点，以提供有助于质子梯度的矢量电荷转移。在这篇综述中，我们讨论了与bc1复合物周转相关的问题，这些问题围绕着正常正向和反向反应以及旁路（或短路）反应的计算速率。根据已知结构中氧化还原中心之间距离给出的速率常数，这些似乎排除了在Q(o)位点反应中涉及中间半醌（SQ）的传统电子转移机制。然而，先前的研究强烈表明，SQ是Q(o)位点超氧化物生成中O2的还原剂，这就产生了一个明显的悖论。一种简单的门控机制，其中在Q(o)位点体积内移动的中间SQ是一个必要组成部分，可以通过库仑相互作用很容易地解释观察到的数据，当血红素bL被还原时，这种相互作用可防止SQ阴离子靠近它。这允许快速且可逆的QH2氧化，但阻止快速的旁路反应。该机制非常自然，并且通过实验得到了很好的支持，在这些实验中，关键残基Glu-295的作用已经通过突变进行了测试，该残基通过旋转位移促进质子从该位点转移。
