Membrane potential-controlled inhibition of cytochrome c oxidase by zinc
Membrane potential-controlled inhibition of cytochrome c oxidase by zinc
复制标题
DOI：
10.1074/jbc.m111922200
复制
发表时间：
2002-04-26
影响因子：
4.8
通讯作者：
Ferguson-Miller, S
中科院分区：
文献类型：
--
作者：
Mills, DA;Schmidt, B;Ferguson-Miller, S
像许多电压敏感的离子泵一样，细胞色素c氧化酶被锌抑制。锌与球形红杆菌细胞色素C氧化酶的外表面结合，在膜电位作用下酶被重组为磷脂囊泡时，抑制酶的K-I值小于或等于5um。在没有膜电位和pH梯度的情况下，需要毫摩尔浓度的锌来抑制。这种差异化的抑制导致野生型氧化酶的呼吸控制比从6急剧增加到40。外源锌的抑制作用可被EDTA消除，与细胞色素c结合不竞争，但与质子竞争。在所测试的多种金属中，只有Cd~(2+)表现出与锌~(2+)类似的抑制作用。对于锌来说，质子泵的速度更慢，效率也更低。结果表明，锌通过质子退出途径抑制了质子的运动，从而允许质子在高膜电位下反向泄漏。从能量转导效率的调节角度，讨论了质子运动在出口通路中的生理和机制意义以及锌对其的阻断作用。
Like many voltage-sensitive ion pumps, cytochrome c oxidase is inhibited by zinc. Binding of zinc to the outside surface of Rhodobacter sphaeroides cytochrome c oxidase inhibits the enzyme with a K-I, of less than or equal to 5 muM when the enzyme is reconstituted into phospholipid vesicles in the presence of a membrane potential. In the absence of a membrane potential and a pH gradient, millimolar concentrations of zinc are required to inhibit. This differential inhibition causes a dramatic increase in the respiratory control ratio from 6 to 40 for wild-type oxidase. The external zinc inhibition is removed by EDTA and is not competitive with cytochrome c binding but is competitive with protons. Only Cd2+ of the many metals tested (Mg2+, Mn2+, Ca2+, Ba2+, Li2+, Cs2+, Hg2+, Ni2+, Co2+, Cu2+ Tb3+, Tm3+) showed inhibitory effects similar to Zn2+. Proton pumping is slower and less efficient with zinc. The results suggest that zinc inhibits proton movement through a proton exit path, which can allow proton back-leak at high membrane potentials. The physiological and mechanistic significance of proton movement in the exit pathway and its blockage by zinc is discussed in terms of regulation of the efficiency of energy transduction.