Inhibition of electron transfer in the cytochrome b-c, segment of the mitochondrial respiratory chain by a synthetic analogue of ubiquinone.
Inhibition of electron transfer in the cytochrome b-c, segment of the mitochondrial respiratory chain by a synthetic analogue of ubiquinone.
复制标题
通过泛醌的合成类似物抑制细胞色素 b-c（线粒体呼吸链的片段）中的电子转移。
DOI：
10.1007/bf00744680
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发表时间：
1980
影响因子：
3
通讯作者：
Haggerty,JG
中科院分区：
文献类型：
--
作者：
Trumpower,BL;Haggerty,JG
泛醌的合成类似物 5-n-十一烷基-6-羟基-4,7-二氧苯并噻唑可抑制大鼠肝线粒体对琥珀酸和 NADH 连接底物的氧化。在 ADP 存在（状态 3）和不存在（状态 4）时都会发生抑制。利用从牛心脏线粒体分离的琥珀酸-细胞色素还原酶复合物，醌类似物抑制琥珀酸-细胞色素还原酶和泛醇-细胞色素还原酶活性，但不抑制琥珀酸-泛醌还原酶活性。细胞色素还原酶活性的抑制明显取决于 pH 值范围（pH 7-8）。在 pH 7.0 时，抑制发生时表观 Ki≤1×10−8M，而在 pH 8.0 时，表观 Ki 比此大一个数量级以上。 5-n-十一烷基-6-羟基-4,7-二氧代苯并噻唑的分光光度滴定显示出可明显检测到的 pKaat pH 6.5，这归因于 6-羟基的电离。这些结果表明，这种醌衍生物是呼吸链 b-c1 段电子转移的高度特异性和有效的抑制剂。由于结构相似，抑制机制很可能涉及正常泛醌功能的破坏。此外，这种抑制取决于抑制类似物的可电离羟基的质子化或b-c1片段中官能团的质子化。
A synthetic analogue of ubiquinone, 5-n-undecyl-6-hydroxy-4,7-dioxobenzothiazole, inhibits oxidation of succinate and NADH-linked substrates by rat liver mitochondria. Inhibition occurs both in the presence (state 3) and absence (state 4) of ADP. With isolated succinate-cytochromecreductase complex from bovine heart mitochondria the quinone analogue inhibits succinate-cytochromecreductase and ubiquinol-cytochromecreductase activities but does not inhibit succinate-ubiquinone reductase activity. Inhibition of cytochromecreductase activities is markedly dependent on pH in the range pH 7–8. At pH 7.0 inhibition occurs with an apparentKi≤1×10−8M, while at pH 8.0 the apparentKiis more than an order of magnitude greater than this. Spectrophotometric titrations of 5-n-undecyl-6-hydroxy-4,7-dioxobenzothiazole show a visibly detectable pKaat pH 6.5 attributable to ionization of the 6-hydroxy group. These results indicate that this quinone derivative is a highly specific and potent inhibitor of electron transfer in theb-c1segment of the respiratory chain. Because of the structural analogy, it is likely that the mechanism of inhibition involves disruption of normal ubiquinone function. In addition, this inhibition depends on protonation of the ionizable hydroxy group of the inhibitory analogue or on protonation of a functional group in theb-c1segment.