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辅酶Q(10)——其在超氧阴离子/过氧化氢形成中作为促氧化剂的作用及代谢组的调节

Coenzyme Q(10)--its role as a prooxidant in the formation of superoxide anion/hydrogen peroxide and the regulation of the metabolome.

作者信息

Linnane Anthony W, Kios Michael, Vitetta Luis

机构信息

Centre for Molecular Biology and Medicine, Epworth Medical Centre, 185-187 Hoddle Street, Richmond, Melbourne, Vic. 3121, Australia.

出版信息

Mitochondrion. 2007 Jun;7 Suppl:S51-61. doi: 10.1016/j.mito.2007.03.005. Epub 2007 Mar 30.

Abstract

Coenzyme Q10 plays a central role in cellular bioenergy generation and its regulation. Closed membrane systems generate a proton motive force to create transient localized bio-capacitors; the captured energy is used for the synthesis of mitochondrial ATP but also for many other processes, such as metabolite translocations, nerve conduction and a host of other bioenergy requiring processes. Coenzyme Q10 plays a key role in many of these sub-cellular membrane energy generating systems. Integral to this phenomenon is the prooxidant role of coenzyme Q10 in generating the major superoxide anion/hydrogen peroxide second messenger system. This messenger system, largely but not exclusively, arises from coenzyme Q10 semiquinone function; it contributes to the regulation of sub-cellular redox potential levels; transcription/gene expression control; is essential for modulated protein turnover and activation; mediates hormone and growth factor extracellular signaling. The regulated prooxidant formation of the superoxide anion/H2O2 second messenger system is essential for the normal physiological function of the metabolome. The normally functioning metabolome is the expression of a finely tuned dynamic equilibrium comprised of thousands of anabolic and catabolic reactions and all cellular signaling systems must be finely regulated. There is still much to be learnt about the up/down regulation of the H2O2 messenger system. The concept that superoxide anion/H2O2 cause random macromolecular damage is rebutted. The administration of antioxidants to quench the inferred toxicity of these compounds as a therapy for age associated diseases is unsupported by extant mammalian clinical trials and should be subject to serious re-evaluation. The role of ascorbic acid as a beneficial hydrogen peroxide prodrug is discussed.

摘要

辅酶Q10在细胞生物能量生成及其调节过程中发挥着核心作用。封闭的膜系统产生质子动力以创建瞬时局部生物电容器;捕获的能量用于线粒体ATP的合成,但也用于许多其他过程,如代谢物转运、神经传导以及许多其他需要生物能量的过程。辅酶Q10在许多此类亚细胞膜能量生成系统中起着关键作用。这一现象的一个重要方面是辅酶Q10在产生主要的超氧阴离子/过氧化氢第二信使系统中的促氧化作用。这个信使系统在很大程度上但并非完全源于辅酶Q10的半醌功能;它有助于调节亚细胞氧化还原电位水平、转录/基因表达控制;对调节蛋白质周转和激活至关重要;介导激素和生长因子的细胞外信号传导。超氧阴离子/H2O2第二信使系统的调节性促氧化形成对于代谢组的正常生理功能至关重要。正常运作的代谢组是由数千个合成代谢和分解代谢反应组成的精细调节的动态平衡的体现,并且所有细胞信号系统都必须得到精细调节。关于H2O2信使系统的上调/下调仍有许多有待了解之处。超氧阴离子/H2O2会导致随机大分子损伤这一概念遭到反驳。现有哺乳动物临床试验不支持使用抗氧化剂来消除这些化合物的推测毒性作为治疗与年龄相关疾病的方法,对此应进行认真的重新评估。本文还讨论了抗坏血酸作为一种有益的过氧化氢前药的作用。

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