ION GRADIENTS AND METABOLIC ENERGY IN ANIMAL TISSUE

在1997财政年度，我们的工作探索了热力学和 动力学可以描述复杂系统中的通量控制， 糖酵解（J Biol Chem 1994;269：25502-14）及其与糖酵解的相互作用。 三羧酸（TCA）循环，电子传递和氧化 磷酸化（FASEB J 1995;9：651-8）。 尤其是， 这些研究集中在改变的有限程度上， 在一种所谓的“限速”酶中， 代谢途径 而是对流量的控制， 表型表达，是动力学和热力学的结果， 系统中每个组件的参数。 它遵循这样一个 药物或激素的作用无法理解的分析 简单地根据“信号地”中的一个或组合的变化， 途径。“一个复杂的激素信号通路的例子， 由胰岛素与其受体结合引发，可通过 开发了代谢底物（Am J Cardiol 1997;80：50 A-64 A）。 底物超载，当然，与酗酒特别相关， 其中大部分毒性是由于存在异常水平 正常的代谢底物。 在未来一年， 酒精戒断过程中大脑TCA循环中底物消耗将 探索的目的是找到替代的，非成瘾性的， 治疗。

During FY97 our work exploring the extent to which thermodynamics and kinetics can describe the control of flux in complex systems including glycolysis (J Biol Chem 1994;269: 25502-14) and its interaction with the tricarboxcyclic acid (TCA) cycle, electron transport and oxidative phosphorylation (FASEB J 1995;9:651-8) continued. Most particularly, these studies concentrated upon the limited extent to which alterations in a so-called "rate-limiting" enzyme can alter the overall flux in a metabolic pathway. Rather the control of flux, and with it the control of phenotypic expression, is a result of the kinetic and thermodynamic parameters of each component in the system. It follows from such an analysis that the actions of drugs or hormones cannot be understood simply in terms of changes in one or a combination of "signally pathways." An example of how the complex hormonal signally pathways, initiated by binding of insulin to its receptor, may be duplicated by metabolic substrates was developed (Am J Cardiol 1997;80:50A-64A). Substrate overload is, of course, particularly relevant to alcoholism, where much of the toxicity results from the presence of abnormal levels of normal metabolic substrates. In the coming year, the role of substrate depletion in TCA cycle of brain during alcohol withdrawal will be explored with the aim of finding alternative, non-addictive treatments.