Tan A K, Ramsay R R, Singer T P, Miyoshi H
Department of Biochemistry and Biophysics, University of California, San Francisco 94143.
J Biol Chem. 1993 Sep 15;268(26):19328-33.
The ubiquinone pool in mitochondrial membranes serves as an electron carrier between both NADH-coenzyme Q oxidoreductase (Complex I) and succinate-coenzyme Q oxidoreductase (Complex II) and ubiquinol-cytochrome-c oxidoreductase (Complex III). It has been reported (Saitoh, I., Miyoshi, H., Shimizu, R., and Iwamura, H. (1992) Eur. J. Biochem. 209, 73-79) that 2-alkyl-4,6-dinitrophenols compete with exogenous coenzyme Q (Q) to inhibit electron transport through cytochromes b and c1 in mammalian mitochondria as well as in photosystem II. We have probed the similarities and differences in the reaction sites of exogenous Q in all three segments of the respiratory chain using selected 2-alkyl-4,6-dinitrophenols. The inhibition of Q analog reduction by the dinitrophenol derivatives was competitive for Complex I and noncompetitive for Complex II. The inhibition of Complex III was competitive with the pentyl analog, but was uncompetitive with the decyl analog, which may be due to different interactions of the two quinol analogs with Complex III. The degree of inhibition by several of these compounds was comparable for Complexes I and III, but Complex II was inhibited to a much smaller extent. The inhibitory potency of these compounds for Complexes I and III was increased by branching and by lengthening the carbon chain at the 2-position equivalent to the isoprenoid side chain of ubiquinone. Hydrophobic substituents increased the inhibition of Complex II. Replacement of the phenolic OH group by a chlorine atom decreased the maximum inhibition of Complex III, but increased that of Complex I. These data suggest that the structures of the exogenous Q-binding sites in Complexes I and III may be similar, but not identical, and that they are different from that in Complex II.
线粒体膜中的泛醌池作为电子载体，在NADH-辅酶Q氧化还原酶（复合体I）、琥珀酸-辅酶Q氧化还原酶（复合体II）以及泛醇-细胞色素c氧化还原酶（复合体III）之间发挥作用。据报道（斋藤一、三好博、清水润、岩村浩，《欧洲生物化学杂志》，1992年，第209卷，第73 - 79页），2-烷基-4,6-二硝基苯酚可与外源性辅酶Q（Q）竞争，抑制哺乳动物线粒体以及光系统II中通过细胞色素b和c1的电子传递。我们使用选定的2-烷基-4,6-二硝基苯酚，探究了呼吸链所有三个部分中外源性Q反应位点的异同。二硝基苯酚衍生物对Q类似物还原的抑制作用，对复合体I是竞争性的，对复合体II是非竞争性的。对复合体III的抑制作用，与戊基类似物是竞争性的，但与癸基类似物是非竞争性的，这可能是由于两种喹醇类似物与复合体III的相互作用不同。其中几种化合物对复合体I和III的抑制程度相当，但对复合体II的抑制程度要小得多。这些化合物对复合体I和III的抑制效力，通过在与泛醌类异戊二烯侧链等效的2位分支和延长碳链而增强。疏水取代基增强了对复合体II的抑制作用。用氯原子取代酚羟基，降低了对复合体III的最大抑制作用，但增强了对复合体I的抑制作用。这些数据表明，复合体I和III中外源性Q结合位点的结构可能相似但不相同，且与复合体II中的不同。
