Membranes and metabolism: insights from invertebrates and lower vertebrates

拟议的研究使用动物模型来确定膜/蛋白质相互作用如何参与代谢的区室化和调节。我的科学方法的一个重要方面是试图将几个层次的组织（整个动物，组织，细胞，细胞器和分子）与建立膜及其嵌入的蛋白质是如何设计的连接这些层次的组织的广泛目标联系起来。我有三个重点领域第二个涉及膜和它们的相关蛋白质.为此，我们将集中在两个膜蛋白的巨大重要性，所有动物细胞（Na/K ATP酶（NKA）和细胞色素c氧化酶（CCO））。NKA是一种消耗ATP的离子泵，据估计约占典型细胞能量需求（ATP）的25%，而CCO是ATP产生电子传递链（ETC）的一部分，负责85%的有氧ATP产生。这两种蛋白质存在于非常不同的膜中（分别为无胆固醇的线粒体膜和富含胆固醇的质膜）。因此，这两个模型捕捉到了膜和代谢之间联系的许多重要元素。 第三个重点领域涉及氮代谢从整个生物体到细胞和亚细胞水平的区室化和动力学。两者合计，拟议的研究将提供一个更好的理解膜脂质/蛋白质相互作用是如何参与介导的ATP生产和ATP消耗过程中的细胞。在更高的组织水平上，他们将建立一些“规则”，用于设计血液和组织之间的代谢物交换。我们目前对这些现象的理解是初步的，因此这些研究将广泛适用于所有多细胞动物。

The proposed research uses animal models to establish how membrane/protein interactions are involved in the compartmentation and regulation of metabolism. An important aspect of my scientific approach is to attempt to relate several levels of organization (whole animal, tissues, cells, organelles and molecules) with the broad goal of establishing how membranes and their embedded proteins are designed to connect these levels of organization. I have three areas of emphasis Two involve membranes and their associated proteins. For these we will focus on two membrane proteins of enormous importance to all animal cells (Na/K ATPase (NKA) and cytochrome c oxidase (CCO)). NKA is an ATP-consuming ion pump that has been estimated to account for about 25% of the energy needs (ATP) of a typical cell while CCO is part of the ATP producing electron transport chain (ETC) responsible for 85% of aerobic ATP production. These two proteins reside in very different membranes (the cholesterol-free mitochondrial membrane and the cholesterol-rich plasma membrane respectively). These two models thus capture many important elements of the links between membranes and metabolism. The third area of emphasis involves the compartmentation and kinetics of nitrogen metabolism from the whole organism to the cellular and subcellular levels. Taken together the proposed studies will provide a better understanding of the how membrane lipid/protein interactions are involved in mediating the ATP-producing and ATP-consuming processes in cells. At higher levels of organization, they will establish some of the "rules" for the design of exchange of metabolites between the blood and tissues. Our current understanding of these phenomena is rudimentary and thus these studies will be of broad applicability to all multicellular animals.