ION GRADIENTS AND METABOLIC ENERGY IN ANIMAL TISSUE

动物组织中的离子梯度和代谢能

• 批准号: 6431371
• 负责人: richard l veech
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6431371
• 关键词: Krebs' cycle; animal tissue; bioenergetics; brain metabolism; drug withdrawal; ethanol; glycolysis; insulin; insulin receptor; ion transport; oxidative phosphorylation; physical chemical interaction; receptor binding

The energy of the gradients of the nine major inorganic ions in working perfused heart are in near equilibrium with each other, the electrical potential between extra- and intracellular phase and the DG of ATP hydrolysis (Masuda T et al, J Biol Chem 1990;265:20321-34). The metabolism of ethanol increases the resting electrical potential of hepatocytes from 28 to 40 mV (Veech RL et al, Alcoholism Clin Expt Stud 1994;18:1040-56). We have completed a study of the effects of ethanol-induced change in hepatic voltage upon the gradients of all the amino acids between portal vein blood and liver and the gradients of the 9 major inorganic ions between intracellular and extracellular space in rat liver in vivo. To our knowledge, this is the first such study. Our work is also the first to show that the end product of hepatic ethanol metabolism, acetate, completely blocks the gut uptake of l-glutamine. l-Glutamine had been thought to be essential not only for its function as a building block for proteins, but also for its action as a bacterial barrier. The implication of the ability of acetate to inhibit the gut utilization of l-glutamine remains to be determined. Previously, we showed that merely changing the substrate available altered the DG of ATP hydrolysis in heart (Kashiwaya Y et al, Am J Cardiol 1997;80:50A-64A). Since injuries of any sort induce a stereotypic change in cellular ionic distributions wherein the cell gains Na+, loses K+ and swells, these stereotypic changes of injury can possibly be reversed by simple changes in the compositions of fluids administered to victims of injury or burns. As a result of these studies and our suggestions to a panel convened by the Academy of Medicine, a recommendation has been made that investigation of the feasibility of making new resuscitation fluids be initiated (see: Fluid Resuscitation, state of the science for treating combat casualties and civilian injuries, National Academy Press, 1999). The goal is to improve the standard treatment of hemorrhage and burns, which has not changed over the past 50 years. We are collaborating in this effort.

在工作灌注心脏的九个主要无机离子梯度的能量彼此接近平衡，细胞外相和细胞内相之间的电势以及ATP水解的DG之间的电势（Masuda T等，J Biol Chem，J Biol Chem 1990; 265：20321-34）。乙醇的新陈代谢将肝细胞的静息电潜力从28增加到40 mV（Veech RL等人，酒精中毒Clin Expt Stud 1994; 18：1040-56）。我们已经完成了一项研究，研究了乙醇诱导的肝电压变化对门静脉血液和肝脏之间所有氨基酸梯度的影响，以及在体内大鼠肝脏内细胞内和细胞外空间之间9个主要无机离子的梯度。据我们所知，这是第一个这样的研究。 我们的工作也是第一个表明乙醇代谢的最终产物（乙酸盐）完全阻止了l-谷氨酰胺的肠道摄取。 l-谷氨酰胺被认为不仅是其作为蛋白质的基础的功能，而且还因为其作为细菌屏障的作用而言是必不可少的。乙酸盐抑制L-谷氨酰胺肠道肠道利用的能力的含义尚待确定。 以前，我们表明，仅更改可用的底物会改变心脏中ATP水解的DG（Kashiwaya Y等，Am J Cardiol 1997; 80：50a-64a）。由于任何形式的损伤会引起细胞离子分布的刻板印象变化，其中细胞获得了Na+，因此失去K+和膨胀，因此这些损伤的刻板印象变化可以通过对受害者受害者或燃烧的受害者的流体组成的简单变化来逆转。由于这些研究以及我们对医学院召集的小组的建议，已经提出了对制造新的复苏液的可行性的建议（请参阅：液体复苏，治疗战斗人员伤亡和平民伤害的科学状况，国家出版社，国家出版社，1999年）。目的是改善出血和燃烧的标准治疗方法，在过去的50年中，这种治疗方法没有改变。我们正在合作这项工作。