Curi Rui, Newsholme Philip, Marzuca-Nassr Gabriel Nasri, Takahashi Hilton Kenji, Hirabara Sandro Massao, Cruzat Vinicius, Krause Mauricio, de Bittencourt Paulo Ivo Homem
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
School of Biomedical Sciences, Curtin Health Innovation Research Institute (CHIRI), Curtin University, Perth, WA 6845, Australia
Biochem J. 2016 Jul 1;473(13):1845-57. doi: 10.1042/BCJ20160103.
The importance of metabolic pathways for life and the nature of participating reactions have challenged physiologists and biochemists for over a hundred years. Eric Arthur Newsholme contributed many original hypotheses and concepts to the field of metabolic regulation, demonstrating that metabolic pathways have a fundamental thermodynamic structure and that near identical regulatory mechanisms exist in multiple species across the animal kingdom. His work at Oxford University from the 1970s to 1990s was groundbreaking and led to better understanding of development and demise across the lifespan as well as the basis of metabolic disruption responsible for the development of obesity, diabetes and many other conditions. In the present review we describe some of the original work of Eric Newsholme, its relevance to metabolic homoeostasis and disease and application to present state-of-the-art studies, which generate substantial amounts of data that are extremely difficult to interpret without a fundamental understanding of regulatory principles. Eric's work is a classical example of how one can unravel very complex problems by considering regulation from a cell, tissue and whole body perspective, thus bringing together metabolic biochemistry, physiology and pathophysiology, opening new avenues that now drive discovery decades thereafter.
一百多年来，代谢途径对生命的重要性以及参与反应的本质一直困扰着生理学家和生物化学家。埃里克·亚瑟·纽肖姆为代谢调节领域贡献了许多原创性的假设和概念，证明了代谢途径具有基本的热力学结构，并且在动物界的多个物种中存在几乎相同的调节机制。他在20世纪70年代到90年代于牛津大学开展的工作具有开创性，有助于更好地理解整个生命周期中的发育和衰老过程，以及导致肥胖、糖尿病和许多其他病症的代谢紊乱的基础。在本综述中，我们描述了埃里克·纽肖姆的一些原创性工作，其与代谢稳态和疾病的相关性，以及在当前前沿研究中的应用。这些前沿研究产生了大量数据，如果没有对调节原理的基本理解，就极难解读这些数据。埃里克的工作是一个经典例子，展示了如何通过从细胞、组织和全身的角度考虑调节来解决非常复杂的问题，从而将代谢生物化学、生理学和病理生理学结合在一起，开辟了新的途径，这些途径至今仍推动着数十年后的发现。
