Catalytic properties of the mitochondrial NADH-ubiquinone oxidoreductase (complex I) and the pseudo-reversible active/inactive enzyme transition.
Catalytic properties of the mitochondrial NADH-ubiquinone oxidoreductase (complex I) and the pseudo-reversible active/inactive enzyme transition.
复制标题
线粒体 NADH-泛醌氧化还原酶（复合物 I）的催化特性和伪可逆活性/非活性酶转换。
DOI：
10.1016/s0005-2728(98)00026-7
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Vinogradov,AD
中科院分区：
文献类型：
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作者：
Vinogradov,AD
在四分之一个多世纪前撰写的题为《线粒体呼吸链的DPNH脱氢酶》的综合综述中，作者指出：“由于复杂技术的应用，这种不寻常和有趣的酶的特征现在被理解了，至少从广义上讲，文献中长期存在的争论已经得到满意的解决，剩下的问题的解决现在似乎是明确的……”1.五年后，另一位研究复合体的学者指出，‘...’由于这一领域自1963年以来一直没有真正的突破，因此很难找到一种新的方法来研究这一主题：SMP，亚线粒体颗粒；FP，来自络合物I的三个亚单位铁硫黄蛋白；FMN，黄素单核苷酸；FAD，黄素腺嘌呤二核苷酸；Q，泛醌-10；QH，泛喹酚-10；Q，2，3-二甲氧基-5-甲基-6-十烷基苯醌；DB，2，3-二甲氧基-5-甲基-6-戊基苯醌；PB，2，3-二甲氧基-5-甲基-6-戊基苯醌；HEXST-Ž。Mumuthum III；NEM，N-乙基马来酰亚胺；大黄酸，9，10-二氢-4，5-二羟基-9，10-二氧代-2-蒽羧酸)。传真：Q7-095-939-39-55；电子邮件：adv@biochem。传记。密歇根州立大学。苏w x2。引用的两种说法似乎都是正确的。事实上，最近对哺乳动物3，真菌4和原核生物5质子转运NADH-苯醌还原酶结构Wx的研究取得了惊人的进展，揭示了这种多亚基和多氧化还原组分酶的显著复杂性。已经指出，哺乳动物复合体I的40多个不同亚基的总蛋白质序列超过了原核糖体3的Wx组成多肽的组合序列。该酶含有多达10个不同的氧化还原成分：FMN 6，多达7个不同的铁硫wx簇7-10和至少两个结合的泛醌Wx物种11。它们从NADH到本体泛素的电子转移的操作顺序尚不清楚。因此，与最近对络合物III12，13和细胞色素wx氧化酶14，15的详细了解相比，分子内酶的氧化还原化学如何与矢量质子转移相耦合的关键问题仍然是推测的问题。近年来的综述集中在wxwx的结构3-5，铁硫簇合物10，质子转移的可能的wx机制16以及酶3，17的比较分子生物学。作者认为，无论现代
In the comprehensive review entitled ‘The DPNH dehydrogenase of the mitochondrial respiratory chain’written more than quarter of a century ago, the authors stated:‘‘Thanks to the application of sophisticated techniques, the characteristics of this unusual and interesting enzyme are now understood, at least in broad terms, long-standing debates in the literature have been satisfactorily resolved, and the way now seems clear for the solution of the remaining probwx lems...’’1. Five years later another scholar of Complex I has pointed out that ‘‘... since no real breakthrough in the area have occurred since 1963, it is difficult to find a fresh approach to the subject’’Abbreviations: SMP, submitochondrial particles; FP, three subunit iron–sulfur–flavoprotein derived from Complex I; FMN, flavin mononucleotide; FAD, flavin adenine dinucleotide; Q, ubiquinone-10; QH, ubiquinol-10; Q, homologues of2 n ubiquinone having n isoprenoid units in position 6 of quinone ring; DB, 2, 3-dimethoxy-5-methyl-6-decylbenzoquinone; PB, 2, 3-dimethoxy-5-methyl-6-pentylbenzoquinone; HAR, hexam-Ž. mineruthenium III; NEM, N-ethyl-maleimide; rhein, 9, 10-dihydro-4, 5-dihydroxy-9, 10-dioxo-2-anthracene carboxylic acid) Corresponding author. Fax: q7-095-939-39-55; E-mail: adv@ biochem. bio. msu. su w x2. Both cited statements still appear to be correct. Indeed, recent spectacular progress in the structural wx wx studies of the mammalian 3, fungal 4 and prokarywx otic 5 proton-translocating NADH–quinone reductases reveals an outstanding complexity of this multi-subunit and multi-redox component enzyme. It has been pointed out that the total protein sequence in more than 40 different subunits of the mammalian Complex I exceeds the combined sequences of the wx constituent polypeptides of prokaryotic ribosome 3. The enzyme bears up to 10 different redox compowx nents: FMN 6, up to seven distinct iron–sulfur w x clusters 7–10 and at least two bound ubiquinone wx species 11. Their operational sequence in electron transfer from NADH to bulk ubiquinone is not known. Thus, the key question of how the intramolecular enzyme redox chemistry is coupled with the vectorial proton translocation remains a matter of speculation compared to the recent detailed understanding w x achieved for Complex III 12, 13 and cytochrome w x oxidase 14, 15. Reviews during the recent years have focused on w x wx the structure 3–5, iron–sulfur clusters 10, possible wx mechanisms of proton translocation 16 and the comw x parative molecular biology of the enzyme 3, 17. In the author’s opinion, however powerful the modern