Membranes and metabolism: insights from invertebrates and lower vertebrates

该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隔和调节。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如何设计以连接这些组织水平的广泛目标联系起来。我有三个重点领域两个涉及膜及其相关蛋白质。为此，我们将重点关注对所有动物细胞都非常重要的两种膜蛋白（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上（分别是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细胞膜与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的区隔和动力学从整个生物体到细胞和亚细胞水平。综上所述，这些研究将更好地理解膜脂/蛋白相互作用如何参与介导细胞中atp的产生和消耗过程。在更高层次的组织中，他们将为血液和组织之间代谢物交换的设计建立一些“规则”。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.