An account of a century of ATP research

IF 1.9 4区 生物学 Q2 BIOLOGY
Sunil Nath
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引用次数: 0

Abstract

The synthesis of adenosine triphosphate (ATP), the universal biological energy currency, by oxidative phosphorylation and photophosphorylation catalyzed by the FOF1-ATP synthase is the fundamental means of cellular energy generation in animals, plants, and microorganisms. Since the ocean area and the amount of biomass is very large, the formation of ATP and its utilization by the myriad energy-consuming processes in the cell is the principal net chemical reaction taking place on the surface of the earth. This is indeed a most important reaction. How exactly does it occur? Since the development of the famous colorimetric assay for measurement of inorganic phosphate (Pi) in 1925, followed by the discovery of ATP in 1929, an enormous amount of research has been done to understand these intracellular energy-linked processes. I present an account of the major developments on ATP synthesis and hydrolysis in a century of research, and summarize the current state of knowledge. My account focuses on the fields of bioenergetics, muscle contraction and motility in cell life, and covers key aspects of metabolic disease, mitochondrial apoptosis and cell death in relation to ATP and the ATP synthase, and the permeability transition pore. It includes developments at molecular, cellular, and macroscopic levels—ascending into ecology—thanks to the conservative nature of metabolic pathways, with ATP as the universal intermediate in the coupled reactions of biological energy transduction. New, emerging sub-fields on ATP and the Warburg Effect, purinergic signaling, condensates and the role of ATP as a biological hydrotope are discussed briefly, and applications in aging and precision medicine are foreseen. I have divided the subject matter into the following five eras to cover the vast ground. (i)—the beginning era of the 1920s (Section 2), (ii)—an era of trials and trails of the 1930s–1940s (Sections 3.1–3.5), (iii)—an era of population-based biochemistry and enzymology in the 1950s–1980s (Sections 4.1–4.9), (iv)—a high-tech era of the 1990s–2020s of high-resolution structural and single-molecule studies, but also an interdisciplinary era of systems biology that integrates approaches from physics, chemistry, biology, mathematics, and engineering (Sections 5.1–5.15), (v)—future prospects (Section 6). The article works out new explanations—with quantitative equations or physical criteria developed for the first time—that may help resolve longstanding issues in muscle contraction, bioenergetics, and transport. My tryst with ATP during 35-years of research is also described, and the search for a theory with greater numerical accuracy is emphasized. Errors of previous theories are identified and corrected, and apparent contradictions are resolved. The aim is to explain and correctly interpret the cumulative experimental record, check for consistency of theory with experiment, remove the inconsistencies in previous theories, and arrive at a unified molecular theory of energy coupling, transduction, ATP synthesis, and ATP hydrolysis. To conclude, a number of recommendations for the progress of scientific research in interdisciplinary and multidisciplinary areas have been made.
一个世纪以来ATP研究的记录。
三磷酸腺苷(adenosine triphosphate, ATP)是生物通用货币,在FOF1-ATP合成酶的催化下,通过氧化磷酸化和光磷酸化合成ATP,是动物、植物和微生物细胞能量生成的基本手段。由于海洋的面积和生物量非常大,ATP的形成及其在细胞内无数能量消耗过程中的利用是地球表面发生的主要净化学反应。这确实是一个最重要的反应。它究竟是如何发生的?自1925年发明了著名的测定无机磷酸盐(Pi)的比色法以来,紧接着在1929年发现了ATP,人们进行了大量的研究来了解这些细胞内能量相关的过程。我介绍了一个世纪以来ATP合成和水解研究的主要进展,并总结了目前的知识状况。我的研究主要集中在细胞生命中的生物能量学、肌肉收缩和运动性领域,涵盖了与ATP和ATP合成酶有关的代谢疾病、线粒体凋亡和细胞死亡的关键方面,以及渗透过渡孔。它包括在分子、细胞和宏观水平上的发展——上升到生态学——由于代谢途径的保守性,ATP作为生物能量转导耦合反应的普遍中间体。本文简要讨论了ATP和Warburg效应、嘌呤能信号、凝聚物以及ATP作为生物水基的作用等新兴子领域,并展望了ATP在衰老和精准医学方面的应用前景。我将主题分为以下五个时代,以涵盖广阔的领域。(我)——的时代,1920年代开始(第二节),(2)——的时代试验和轨迹的1930年代- 1940年代(章节3.1 - 3.5),(3)——的时代以人群为基础的生物化学和酶学在1950年代- 1980年代(章节4.1 - 4.9)(iv)——1990年代- 2020年代的高科技时代的高分辨率结构和单分子研究,而且一个跨学科的系统生物学时代相结合的方法从物理、化学、生物学、数学、和工程(章节5.1 - 5.15),(v)-未来前景(第6条)。这篇文章提出了新的解释——首次使用定量方程或物理标准——这可能有助于解决肌肉收缩、生物能量学和运输方面长期存在的问题。本文还描述了我在35年的研究中与ATP的幽会,并强调了对具有更高数值精度的理论的探索。发现和纠正了以往理论的错误,解决了明显的矛盾。目的是解释和正确解释累积的实验记录,检查理论与实验的一致性,消除以往理论中的不一致之处,得出一个统一的能量耦合、转导、ATP合成和ATP水解的分子理论。最后,对跨学科和多学科领域的科学研究进展提出了一些建议。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Biosystems
Biosystems 生物-生物学
CiteScore
3.70
自引率
18.80%
发文量
129
审稿时长
34 days
期刊介绍: BioSystems encourages experimental, computational, and theoretical articles that link biology, evolutionary thinking, and the information processing sciences. The link areas form a circle that encompasses the fundamental nature of biological information processing, computational modeling of complex biological systems, evolutionary models of computation, the application of biological principles to the design of novel computing systems, and the use of biomolecular materials to synthesize artificial systems that capture essential principles of natural biological information processing.
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