A competitive inhibition of the mitochondrial NADH-ubiquinone oxidoreductase (complex I) by ADP-ribose.
A competitive inhibition of the mitochondrial NADH-ubiquinone oxidoreductase (complex I) by ADP-ribose.
复制标题
ADP-核糖对线粒体 NADH-泛醌氧化还原酶（复合物 I）的竞争性抑制。
DOI：
10.1016/s0005-2728(97)00029-7
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发表时间：
1997
期刊：
影响因子：
--
通讯作者：
Vinogradov,AD
中科院分区：
文献类型：
--
作者：
Zharova,TV;Vinogradov,AD
不同浓度的NAD+对牛心脏亚线粒体颗粒（SMP）的NADH氧化酶活性的竞争性抑制存在着明显的定量差异。ADP-核糖（ADPR）被鉴定为导致观察到的抑制变化的抑制性污染物质。ADPR竞争性抑制NADH氧化，SMP、纯化复合物I和三亚基NADH脱氢酶（FP）的Ki值（25°C，pH 8.0）分别为26 μM、30 μM和180 μM。ADPR可降低NADH诱导的黄素还原反应，抑制FP在好氧氧化过程中的循环漂白。ADPR抑制SMP鱼藤酮敏感性NADH氧化酶的Ki不依赖于Δ μ OH+。琥珀酸盐还原NAD+的初始速率对ADPR不敏感。该抑制剂增加了NAD+还原的稳态水平，在有氧琥珀酸支持的紧密耦合SMP催化的反向电子转移过程中达到。所得结果与线粒体NADH-泛醌还原酶催化的直接和逆反应中不同核苷酸结合位点的提议一致。
Considerable quantitative variations in the competitive inhibition of NADH oxidase activity of bovine heart submitochondrial particles (SMP) by different samples of NAD+were observed. ADP-ribose (ADPR) was identified as the inhibitory contaminating substance responsible for variations in the inhibition observed. ADPR competitively inhibits NADH oxidation with Kivalues (25°C, pH 8.0) of 26 μM, 30 μM, and 180 μM for SMP, purified Complex I and three-subunit NADH dehydrogenase (FP), respectively. ADPR decreases NADH-induced flavin reduction and prolongs the cyclic bleaching of FP during aerobic oxidation of NADH. Kifor inhibition of the rotenone-sensitive NADH oxidase in SMP by ADPR does not depend on Δ μ ̄H+. The initial rate of the energy-dependent NAD+reduction by succinate is insensitive to ADPR. The inhibitor increases the steady-state level of NAD+reduction reached during aerobic succinate-supported reverse electron transfer catalyzed by tightly coupled SMP. The results obtained are consistent with the proposal on different nucleotide-binding sites operating in the direct and reverse reactions catalyzed by the mitochondrial NADH-ubiquinone reductase.