Inhibition by nitroso-chloramphenicol of the proton translocation in mitochondria.
Inhibition by nitroso-chloramphenicol of the proton translocation in mitochondria.
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亚硝基氯霉素抑制线粒体中的质子易位。
DOI：
10.1016/0006-2952(82)90298-2
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发表时间：
1982
影响因子：
5.8
通讯作者：
Yunis,AA
中科院分区：
文献类型：
--
作者：
Abou-Khalil,S;Abou-Khalil,WH;Yunis,AA
我们最近发现，与氯霉素（CAP）不同，其硝基还原衍生物亚硝基氯霉素（NO-CAP）表现为线粒体中能量保存机制的有效抑制剂[Abou-Khalilet等，Biochem.Pharmac.29，2605（1980）]。分别需要75和250 μM的NO-CAP浓度才能抑制谷氨酸和琥珀酸的ATP形成，而相似的CAP浓度则没有影响。测试与ATP生物合成相关的几个关键反应，发现抑制浓度的NO-CAP干扰如下：（a）NAD连接底物的转运（如谷氨酸）进入线粒体仅被部分抑制，而FAD连接的底物（B）Pi的转运仅被抑制约50%，（c）线粒体ADP的转运完全不受影响，（d）线粒体ADP的转运仅被抑制约50%，（e）线粒体ADP的转运仅被抑制约50%，（f）线粒体ADP的转运仅被抑制约50%。（d）ATP酶活性（在解偶联剂存在下通过Pi释放或通过H+排出测量）仅受到轻微影响;（e）在磷酸化或无磷酸化条件下以及在没有Pi的情况下，发现NO-CAP完全阻断由琥珀酸或谷氨酸氧化引起的线粒体H+排出;然而，在相似的条件下，两种底物的氧化没有被完全抑制。根据先前的数据和目前的实验表明Piagainst NO-CAP对呼吸的影响，NO-CAP与反应性线粒体巯基干扰的可能性进行了讨论。此外，NO-CAP相比，传统的氧化磷酸化抑制剂（如鱼藤酮，抗霉素A，寡霉素，mersalyl和其他）似乎有一个独特的模式，该过程的行动。结果表明，NO-CAP的抑制作用主要位于呼吸链水平，质子转运活动被完全阻断。
We have found recently that, unlike chloramphenicol (CAP), its nitroreduction derivative nitroso-chloramphenicol (NO-CAP) behaved as a potent inhibitor of the energy-conserving mechanism in mitochondria [Abou-Khalilet al. Biochem. Pharmac.29,2605 (1980)]. Concentrations of 75 and 250 μM NO-CAP were required to inhibit ATP formation with glutamate and succinate, respectively, whereas similar CAP concentrations were without effect. Testing several key reactions associated with the biosynthesis of ATP, inhibitory concentrations of NO-CAP were found to interfere as follows: (a) the transport of an NAD-linked substrate (e.g. glutamate) into mitochondria was only partially inhibited, whereas that of an FAD-linked substrate (e.g. succinate) was not inhibited but was rather slightly activated; (b) the transport of Piwas only inhibited at about 50%; (c) mitochondrial ADP transport was not affected at all; (d) the ATPase activity, measured either by Pi release in the presence of an uncoupler or by H+ejection, was only slightly affected; and (e) under either phosphorylation or no phosphorylation conditions and in the absence of Pi, NO-CAP was found to completely block mitochondrial H+extrusion resulting from the oxidation of either succinate or glutamate; however, under similar conditions the oxidation of the two substrates was not totally inhibited. The possibility of interference by NO-CAP with reactive mitochondrial thiols groups is discussed in the light of previous data and current experiments showing protection by Piagainst NO-CAP effects on respiration. Moreover, NO-CAP as compared to conventional inhibitors of oxidative phosphorylation (e.g. rotenone, antimycin A, oligomycin, mersalyl and others) appeared to have a distinct mode of action on that process. The results demonstrate that the inhibitory effect of NO-CAP is primarily located at the respiratory chain level where the proton translocation activity is fully blocked.