Non-linear inhibition curves for tight-binding inhibitors of dimeric ubiquinol-cytochrome c oxidoreductases. Evidence for rapid inhibitor mobility.
Non-linear inhibition curves for tight-binding inhibitors of dimeric ubiquinol-cytochrome c oxidoreductases. Evidence for rapid inhibitor mobility.
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二聚泛醇-细胞色素 c 氧化还原酶紧密结合抑制剂的非线性抑制曲线。
DOI：
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发表时间：
1992
期刊：
影响因子：
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通讯作者：
P. Rich
中科院分区：
文献类型：
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作者：
G. Bechmann;H. Weiss;P. Rich
本文研究了在浓度递增的抗霉素A、夫尼库洛辛和/或粘噻唑存在下，粗糙脉孢菌和牛心线粒体中游离的二聚体bc 1复合物（泛醇-细胞色素c氧化还原酶）的稳态电子流和电子传递。根据所用的不同喹啉和抑制剂，获得抛物线或线性抑制曲线。当抑制剂直接影响速率决定步骤时，出现线性曲线。抛物线曲线的最合理的解释是疏水抑制剂抗霉素A，funiculosin（速率小于500 s-1）和myxothiazol（速率大于1 s-1）的快速二聚体内交换。利用牛心线粒体，如果醌醇-O_2氧化还原酶在300 s ~（-1）左右翻转，则抗霉素A的抑制曲线为抛物线，双曲线滴定曲线可能是二聚体内和二聚体间再分布的结果（速率约100 s-1）的抑制剂之间的酶纳入连续的磷脂膜。这一解释得到了从荚膜红细菌中获得的色素的实验的支持。如最近描述的[Fernando-Velasco，J. R.（1992）Biophys. J. 2，A153]，细胞色素B在亚化学计量浓度的抗霉素A闪光后1 s内完全再氧化。这种缓慢再氧化的动力学可以用二聚体内和二聚体间的再分布来表示，其速率常数分别约为10 s-1和2 x 10（6）M-1 s-1。看来，快速抑制剂重新分布可能是一个普遍的现象，疏水性抑制剂的酶纳入脂膜。
Steady-state electron flow through and electron delivery into isolated dimeric bc1 complex (ubiquinol--cytochrome c oxidoreductase) from Neurospora crassa and beef heart mitochondria were studied in the presence of increasing concentrations of antimycin A, funiculosin and/or myxothiazol. Parabolic or linear inhibition curves were obtained, depending upon the different quinols and inhibitors that were used. Linear curves occur when the inhibitor directly affects the rate-determining step. The most reasonable explanation for the parabolic curves is given by a fast intradimeric exchange of the hydrophobic inhibitors antimycin A, funiculosin (rate less than 500 s-1) and of myxothiazol (rate greater than 1 s-1). Using mitochondria from beef heart, the shape of the inhibition curve with antimycin A is parabolic if the quinol--O2 oxidoreductase turns over at about 300 s-1, but hyperbolic if the rate is 5 times less. The hyperbolic titration curve may be the result of both intradimeric and an additional interdimeric redistribution (rate approximately 100 s-1) of inhibitors between enzymes incorporated in a continuous phospholipid membrane. This explanation is supported by experiments with chromatophores obtained from Rhodobacter capsulatus. As recently described [Fernandez-Velasco, J. & Crofts, A. R. (1992) Biophys. J. 2, A153], cytochrome b becomes fully reoxidized within 1 s after a flash at substoichiometric concentrations of antimycin A. This kinetic of the slow reoxidation can be expressed in terms of the intradimeric and interdimeric redistribution with rate constants of about 10 s-1 and 2 x 10(6) M-1 s-1, respectively. It seems that rapid inhibitor redistribution may be a widespread phenomenon for hydrophobic inhibitors of enzymes incorporated in lipid membranes.
DOI：
10.1128/mmbr.54.2.101-129.1990
发表时间：
1990-06
期刊：
Microbiological reviews
影响因子：
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作者：
B. Trumpower
通讯作者：
B. Trumpower