OXYGEN AND PH DEPENDENCE OF CELLULAR METABOLISM

细胞代谢的氧气和 PH 依赖性

• 批准号: 3270564
• 负责人: DAVID F WILSON
• 金额: $ 18.13万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 1974
• 资助国家: 美国
• 起止时间: 1974-11-01 至 1989-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3270564
• 关键词: acid base balance; adenosine triphosphate; bioenergetics; biological transport; cell biology; cellular respiration; cytochrome c; eicosanoid metabolism; electron transport; epinephrine; fatty acid biosynthesis; glucagon; gluconeogenesis; heart metabolism; hormone regulation /control mechanism; isolation perfusion; liver cells; mitochondria; oxidation reduction reaction; oxygen consumption; oxygen tension; thermodynamics; tissue /cell culture; vascular endothelium

All cellular metabolism, i.e. anabolism, catabolism and transport, is intimately coupled to the cellular energy level as expressed in the [ATP]/[ADP][Pi]. Mitochondrial oxidative phosphorylation is primarily responsible for maintaining the energy level and it thereby strongly influences all other metabolism. Our objective is to gain an understanding of the regulation of cellular metabolism and in this project we will concentrate on the role of oxygen and intracellular pH in metabolic homeostasis. In order to approach this general question we will: 1. Examine the oxygen dependence of mitochondrial oxidative phosphorylation in vivo as it is expressed in the cytoplasmic [ATP]/[ADP][Pi] and [NAD]/[NADH], the mitochondrial [NAD]/[NADH] and in the behavior of the energy requiring metabolic reactions such as gluconeogenesis, urea synthesis and protein synthesis. 2. Examine the proposal that mitochondrial oxidative phosphorylation is the primary oxygen sensor for regulation of tissue oxygen tension through control of local vascular resistance. 3. Measure the oxygen dependence of prostaglandin synthesis by cultured endothelial cells. 4. Establish the relationship of intracellular to extracellular pH in suspensions of isolated hepatocytes and then determine the pH dependence of gluconeogenesis, urea synthesis, respiration, [ATP]/[ADP][Pi], etc. The dependence of regulatory hormone function (norepinephyrine, glucagon) on intra and extracellular pH will also be measured. 5. Measure in vitro dependence of the apparent Km for oxygen on pH, [ATP]/[ADP][Pi] and reduction of cytochrome c using suspensions of isolated mitochondria.

所有的细胞代谢，即促排、促排和转运， 与细胞能量水平密切相关， [ATP]/[ADP][Pi]。 线粒体氧化磷酸化主要是 负责维持能量水平， 影响所有其他新陈代谢。 我们的目标是了解 细胞代谢调节的研究，在本项目中，我们将 专注于氧和细胞内pH在代谢中的作用 体内平衡。 为了解决这个问题，我们将：1。 检测线粒体氧化磷酸化的氧依赖性， 体内，因为它在细胞质[ATP]/[ADP][Pi]中表达， [NAD][2019 - 05 - 15][2019 - 05][2019 - 0 需要能量的代谢反应，如代谢生成、尿素 合成和蛋白质合成。 2.审查建议， 线粒体氧化磷酸化是主要的氧传感器， 通过控制局部血管调节组织氧分压 阻力 3.测量前列腺素合成的氧依赖性， 培养的内皮细胞。 4.建立细胞内 分离的肝细胞悬液中的细胞外pH值，然后 测定尿素生成，尿素合成， 呼吸、[ATP]/[ADP][Pi]等。调节激素依赖性 功能（去甲肾上腺素，胰高血糖素）对细胞内和细胞外pH值将 也要衡量。 5.测量表观Km的体外依赖性， 氧对pH、[ATP]/[ADP][Pi]和细胞色素c还原的影响， 分离的线粒体的悬浮液。