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The murburn precepts for aerobic respiration and redox homeostasis
Progress in Biophysics and Molecular Biology ( IF 3.2 ) Pub Date : 2021-06-10 , DOI: 10.1016/j.pbiomolbio.2021.05.010
Kelath Murali Manoj 1 , N M Bazhin 2
Affiliation  

Murburn concept is a new perspective to metabolism which posits that certain redox enzymes/proteins mediate catalysis outside their active site, via diffusible reactive oxygen species (DROS, usually deemed as toxic wastes). We have recently questioned the proton-centric chemiosmotic rotary ATP synthesis (CRAS) explanation for mitochondrial oxidative phosphorylation (mOxPhos) and proposed an oxygen-centric murburn model in lieu. Herein, the chemical equations and thermodynamic foundations for this new model of mOxPhos are detailed. Standard transformed Gibbs free energy values of respiratory reactions are calculated to address the spontaneity, control, and efficiency of oxidative phosphorylation. Unlike the deterministic/multi-molecular and ‘irreducibly complex’ CRAS model, the stochastic/bimolecular and parsimonious murburn reactions afford a more viable precept for the variable and non-integral stoichiometry, higher yield for NADH than FADH2, and origin/evolution of oxygen-centric cellular life. Also, we present tangible DROS-based explanations for the multiple roles of various reaction components, HCN > H2S order of cellular toxicity in aerobes, and explain why oxygen inhibits anaerobes. We highlight the thermodynamic significance of proton deficiency in NADH/mitochondria and link the ‘oxygen → DROS → water’ metabolic pathway to the macroscopic physiologies of ATP-synthesis, trans-membrane potential, thermogenesis, and homeostasis. We also provide arguments for the extension of the murburn bioenergetics model to life under anoxic and extreme/unique habitats. In the context of mOxPhos, our findings imply that DROS should be seen as an essential requisite for life, and not merely as pathophysiological manifestations.



中文翻译:

有氧呼吸和氧化还原稳态的默本戒律

Murburn 概念是新陈代谢的新观点,它假定某些氧化还原酶/蛋白质通过可扩散的活性氧(DROS,通常被认为是有毒废物)在其活性位点外介导催化。我们最近质疑了以质子为中心的化学渗透旋转 ATP 合成 (CRAS) 对线粒体氧化磷酸化 (mOxPhos) 的解释,并提出了以氧为中心的 murburn 模型。本文详细介绍了这种新的 mOxPhos 模型的化学方程式和热力学基础。计算呼吸反应的标准转换吉布斯自由能值以解决氧化磷酸化的自发性、控制和效率。与确定性/多分子和“不可还原的复杂”CRAS 模型不同,2,以及以氧为中心的细胞生命的起源/进化。此外,我们对各种反应组分的多重作用(HCN > H 2 S 在需氧菌中的细胞毒性顺序)提出了切实的基于 DROS 的解释,并解释了为什么氧气会抑制厌氧菌。我们强调了 NADH/线粒体中质子缺乏的热力学意义,并将“氧 → DROS → 水”代谢途径与 ATP 合成、跨膜电位、产热和体内平衡的宏观生理学联系起来。我们还为将 murburn 生物能量学模型扩展到缺氧和极端/独特栖息地下的生命提供了论据。在 mOxPhos 的背景下,我们的研究结果表明 DROS 应该被视为生命的基本必需品,而不仅仅是病理生理表现。

更新日期:2021-06-10
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