SUBSTRATE, PROTEIN, AND AMINO ACID METABOLISM

底物、蛋白质和氨基酸代谢

• 批准号: 6240396
• 负责人: JOHN F BURKE
• 金额: $ 44.37万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-12-01 至 1997-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6240396
• 关键词: Krebs' cycle; adult human (21+); aminoacid biosynthesis; aminoacid metabolism; bioenergetics; burns; child (0-11); disease /disorder model; dogs; enzyme substrate; gastrointestinal function; gluconeogenesis; human subject; inflammation; laboratory rabbit; liver metabolism; muscle metabolism; nitrogen balance; nitrogen metabolism; nuclear magnetic resonance spectroscopy; positron emission tomography; protein metabolism; radiotracer; urea cycle

Increased loss of body protein (nitrogen) particularly from skeletal muscles, with the development of a profound catabolic state with extensive alteration of the amino acid, glucose and energy economy of the individual are characteristics of a major burn injury. These compromise cell function, organ function, host defense and, increase morbidity. They have proven difficult to reverse and contemporary nutritional thera- peutic modalities have been ineffective. Through application of stable nuclide tracer techniques, the specific aims of this project are: (a) to reduce muscle protein wasting in burn injury through understanding of muscle, gut, liver amino acid substrate interactions including investigation of carbon skeletal exchanges, nitrogen trafficking and urea production [Studies include the characterization of whole body and limb amino acid kinetics in burn patients and detailed studies of interorgan (gut/liver, muscle, kidney) amino acid metabolism in a chronically catheterized animal model]; (b) to define arginine, ornithine, citrulline kinetics with particular reference to nitric oxide production during uncomplicated and complicated burn illness; (c) to characterize the simultaneous changes in amino acid fluxes across muscle gut and liver, including a quantitation of fluxes of Krebs cycle intermediates and rates of carbon entry into the cycle, using animal models and a combination of NMR, mass-spectrometry and the cylotron to identify labeling of derivatives of glutamate and lactate; and (d) to continue an exploration of the role played by glutamate, cysteine, tyrosine, arginine and proline as "conditionally essential" amino acids, including estimations of their rates of de novo synthesis with the potential benefit for the amino acid economy emerging from the administration of cystine and tyrosine etc. in dipeptide form. These aims will be accomplished via a series of interrelated metabolic investigations in healthy adults and burn patients, supplemented with studies using experimental animal models. These studies will exploit classic mass spectrometric techniques supplemented by innovative combined NMR and cyclotron techniques adding considerable specificity and sensitivity. New and exciting information concerning the in vivo interorgan metabolic regulation and interorgan utilization of specific amino acids in human subjects is expected, allowing formulation and evaluation of nutritional/therapeutic modalities designed to reduce morbidity and mortality.

人体蛋白质损失增加（氮），特别是骨骼的损失 肌肉，随着深刻的分解代谢状态与 氨基酸，葡萄糖和能源经济的广泛改变 个体是重大烧伤的特征。 这些妥协 细胞功能，器官功能，宿主防御并增加发病率。 事实证明，它们很难逆转和当代营养thera- 精神的方式无效。 通过稳定的应用 核素示踪剂技术，该项目的具体目的是：（a）到 通过了解 肌肉，肠道，肝氨基酸底物相互作用，包括 调查碳骨骼交换，氮贩运和尿素 生产[研究包括整个身体和肢体的表征 烧伤患者的氨基酸动力学和详细研究 （肠道/肝脏，肌肉，肾脏）长期氨基酸代谢 导管动物模型]； （b）定义精氨酸，鸟嘌呤，瓜氨酸 动力学特别参考一氧化氮在 简单而复杂的烧伤疾病； （c）表征 同时改变肌肉肠道和肝脏的氨基酸通量， 包括定量克雷布斯循环中间体和速率 使用动物模型和组合的碳进入周期的碳进入周期 NMR，质谱法和质量器，以识别标记的标记 谷氨酸和乳酸的衍生物； （d）继续探索 谷氨酸，半胱氨酸，酪氨酸，精氨酸和脯氨酸的作用 作为“有条件必不可少的”氨基酸，包括对其的估计 从头合成的速率具有氨基酸的潜在益处 经济从胱氨酸和酪氨酸等管理中出现 二肽形式。 这些目标将通过一系列 在健康成年人中进行了相互关联的代谢研究和燃烧 患者补充了使用实验动物模型的研究。 这些研究将利用经典的质谱技术 补充创新的NMR和回旋技术添加 相当大的特异性和灵敏度。 新的令人兴奋的信息 关于体内跨组织代谢调节和跨组织 预计在人类受试者中利用特定氨基酸， 允许制定和评估营养/治疗方式 旨在降低发病率和死亡率。