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琥珀酸在缺血中的来源:它来自哪里?

Succinate in ischemia: Where does it come from?

机构信息

Department of Medical Biochemistry, Semmelweis University, Tuzolto st. 37-47, Budapest, 1094, Hungary.

出版信息

Int J Biochem Cell Biol. 2019 Oct;115:105580. doi: 10.1016/j.biocel.2019.105580. Epub 2019 Aug 5.

DOI:10.1016/j.biocel.2019.105580
PMID:31394174
Abstract

During tissue ischemia succinate accumulates. Herein, literature spanning the past nine decades is reviewed leaning towards the far greater role of Krebs cycle's canonical activity yielding succinate through α-ketoglutarate -> succinyl-CoA -> succinate even in hypoxia, as opposed to reversal of succinate dehydrogenase. Furthermore, the concepts of i) a diode-like property of succinate dehydrogenase rendering it difficult to reverse, and ii) the absence of mammalian mitochondrial quinones exhibiting redox potentials in the [-60, -80] mV range needed for fumarate reduction, are discussed. Finally, it is emphasized that a "fumarate reductase" enzyme entity reducing fumarate to succinate found in some bacteria and lower eukaryotes remains to be discovered in mammalian mitochondria.

摘要

在组织缺血期间,琥珀酸积累。本文综述了过去九十年的文献,倾向于认为克雷布斯循环的经典活性通过α-酮戊二酸->琥珀酰辅酶 A->琥珀酸产生琥珀酸的作用要大得多,即使在缺氧情况下也是如此,而不是琥珀酸脱氢酶的逆转。此外,还讨论了琥珀酸脱氢酶的 i)二极管样特性使其难以逆转,以及 ii)哺乳动物线粒体醌不存在还原电位在[-60,-80] mV 范围内,这是需要琥珀酸还原的条件,的概念。最后,强调了在哺乳动物线粒体中仍然需要发现某些细菌和低等真核生物中发现的将延胡索酸还原为琥珀酸的“延胡索酸还原酶”酶实体。

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1
Succinate in ischemia: Where does it come from?琥珀酸在缺血中的来源:它来自哪里?
Int J Biochem Cell Biol. 2019 Oct;115:105580. doi: 10.1016/j.biocel.2019.105580. Epub 2019 Aug 5.
2
Accumulation of Succinate in Cardiac Ischemia Primarily Occurs via Canonical Krebs Cycle Activity.心脏缺血时琥珀酸的积累主要通过经典的克雷布斯循环活动发生。
Cell Rep. 2018 May 29;23(9):2617-2628. doi: 10.1016/j.celrep.2018.04.104.
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Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS.琥珀酸的缺血性积累通过线粒体活性氧控制再灌注损伤。
Nature. 2014 Nov 20;515(7527):431-435. doi: 10.1038/nature13909. Epub 2014 Nov 5.
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Fumarate reductase activity maintains an energized membrane in anaerobic Mycobacterium tuberculosis.延胡索酸还原酶活性维持厌氧结核分枝杆菌的高能膜。
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Genetic characterization of a single bifunctional enzyme for fumarate reduction and succinate oxidation in Geobacter sulfurreducens and engineering of fumarate reduction in Geobacter metallireducens.嗜硫还原地杆菌中用于富马酸还原和琥珀酸氧化的单一双功能酶的遗传特征及嗜金属还原地杆菌中富马酸还原的工程改造
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Schistosoma mansoni sporocysts contain rhodoquinone and produce succinate by fumarate reduction.曼氏血吸虫孢子蚴含有泛醌,并通过富马酸还原产生琥珀酸。
Parasitology. 1997 Aug;115 ( Pt 2):177-82. doi: 10.1017/s003118209700125x.
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The succinate mechanism of insulin release.胰岛素释放的琥珀酸机制。
Diabetes. 2002 Sep;51(9):2669-76. doi: 10.2337/diabetes.51.9.2669.
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Unsuspected task for an old team: succinate, fumarate and other Krebs cycle acids in metabolic remodeling.一个老团队的意外任务:琥珀酸、富马酸及其他三羧酸循环酸在代谢重塑中的作用
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Enzyme electrokinetics: energetics of succinate oxidation by fumarate reductase and succinate dehydrogenase.酶促动力学:延胡索酸还原酶和琥珀酸脱氢酶催化琥珀酸氧化的能量学
Biochemistry. 2001 Sep 18;40(37):11234-45. doi: 10.1021/bi010889b.
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The covalent attachment of FAD to the flavoprotein of Saccharomyces cerevisiae succinate dehydrogenase is not necessary for import and assembly into mitochondria.黄素腺嘌呤二核苷酸(FAD)与酿酒酵母琥珀酸脱氢酶黄素蛋白的共价连接对于其导入和组装到线粒体中并非必需。
Eur J Biochem. 1994 Jun 15;222(3):983-90. doi: 10.1111/j.1432-1033.1994.tb18949.x.

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