Department of Biochemical Engineering and Biotechnology, Indian Institute of Technology, Delhi, Hauz Khas, New Delhi 110016, India.
Biophys Chem. 2019 Dec;255:106271. doi: 10.1016/j.bpc.2019.106271. Epub 2019 Oct 17.
Adenosine triphosphate (ATP) is the universal biological energy fuel, or nature's gasoline. The vast quantities of ATP required for sustenance of living processes in cells are synthesized by oxidative phosphorylation and photosynthesis. The chemiosmotic theory of energy coupling was proposed by Mitchell more than 50 years ago but has a contentious history. Part of the accumulated body of experimental evidence supports Mitchell's theory, and part of the evidence conflicts with the theory. Although Mitchell's theory was strongly criticized by several prominent scientists, the controversy was never resolved. Certain theoretical arguments and electrostatic calculations were originally made to justify the central tenet of the chemiosmotic theory of electrogenic proton transfer and violation of electrical neutrality in bulk aqueous phases by creation of a delocalized field. However, these calculations have not been scientifically scrutinized previously. Here it is proved from first principles that the original physical arguments and calculations made in support of steady state electrogenic ion transfer and chemiosmosis violate Gauss's law. Nath's two-ion theory of energy coupling in which the field is local, and ion translocation is dynamically electrogenic but overall electroneutral is shown to satisfactorily resolve the difficulties. Characterization of length scales in mitochondrial systems is shown to impose strong constraints on possible mechanisms of energy transduction. Some biological implications for energy coupling, transduction and ATP synthesis arising as a result of the above analysis are discussed. Examples of several other biological processes where the new theory is useful such as apoptosis, muscle contraction, the joint multisite regulation of oxidative phosphorylation and the Krebs cycle, and hindered protein aggregation arising from ATP's hydrotropic properties are outlined.
三磷酸腺苷（ATP）是通用的生物能量燃料，或者说是大自然的汽油。细胞中维持生命过程所需的大量 ATP 是通过氧化磷酸化和光合作用合成的。化学渗透能量偶联理论是由 Mitchell 在 50 多年前提出的，但它有着颇具争议的历史。部分积累的实验证据支持 Mitchell 的理论，而部分证据则与该理论相冲突。尽管 Mitchell 的理论受到了几位知名科学家的强烈批评，但争议从未得到解决。某些理论论证和静电计算最初是为了证明电生质子转移的化学渗透理论的中心原则以及在体相水溶液中违反电中性而创建非定域场的合理性。然而，这些计算以前从未受到过科学审查。从第一性原理证明了，最初为支持稳态电生离子转移和化学渗透而做出的物理论证和计算违反了高斯定律。Nath 的双离子能量偶联理论认为，场是局部的，离子易位在动力学上是电生的，但总体上是电中性的，该理论令人满意地解决了这些困难。线粒体系统的特征长度尺度的特征对能量转导的可能机制施加了严格的限制。由于上述分析而产生的能量偶联、转导和 ATP 合成的一些生物学意义进行了讨论。概述了新理论在其他几个生物学过程中的应用，例如细胞凋亡、肌肉收缩、氧化磷酸化和三羧酸循环的多站点联合调节以及 ATP 的亲水性特性引起的蛋白质阻碍聚集。
