Amino Acid Interrelations and Metabolism

氨基酸相互关系和代谢

• 批准号: 7391261
• 负责人: VERNON L YOUNG
• 金额: $ 39.79万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 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/7391261
• 关键词: Acute-Phase Proteins; Affect; Albumins; Amino Acids; Animal Model; Apolipoproteins B; Arginine; Burn injury; Carbon; Catabolism; Cysteine; Enteral; Fibronectins; Functional disorder; Glucose; Glutamates; Glutamine; Glutathione; Glutathione Metabolism Pathway; Glycine; Homocysteine; Homocystine; Investigation; Kidney; Liver; Lung; Maintenance; Mass Spectrum Analysis; Metabolic; Metabolism; Methods; Modeling; Morbidity - disease rate; Nitric Oxide; Nitrogen; Nutritional; Nutritional status; Organ; Oryctolagus cuniculus; Pathway interactions; Patients; Protein Export Pathway; Proteins; Rate; Recovery; Regulation; Research; Role; Series; Staging; Sulfur Amino Acids; Supplementation; cysteine rich protein; design; in vivo; mortality

Alterations in the regulation of energy and amino acid metabolism are of etiological importance in morbidity and mortality of the burn patients. This project involves integrated studies of in vivo aIterations of the metabolism of the so-called 'conditionally indispensable" amino acids, especially glutamate-glutamine, arginine and the sulfur amino acids. The specific aims are: 1) to evaluate the status of glutamine metabolism, in relation to its role in both glucose and energy substrate metabolism and the maintenance of nitrogen (N) economy. This aim will involve studies, in burn patients and healthy control subjects, designed to assess the consequences of enteral and parenteral glutamine supplementation on splanchnic protein and amino acid metabolism. Studies in a burn rabbit model will include use of a hyperglutaminemic clamp and mass spectrometry, to assess the major fate of glutamine in pathways of carbon and N metabolism. 2) to examine the status and nutritional factors, especially the sulfur amino acids, that affect glutathione (GSH) metabolism in burned patients. This aim will include studies in patients and a series of investigations in the burn animal model. We will determine the roles of the conditionally indispensable amino acid precursors of GSH synthesis (glutamate/glutamine, glycine and cysteine) in the regulation of glutathione metabolism after burn injury. 3) to explore the status of arginine metabolism and the regulatory factors of nitric oxide synthesis after burn injury, in relation to organ function (effect of arginine supply and the metabolic modulation of NO synthesis in different organs, especially lungs, liver and kidneys). This aim will include an initial determination of the significance of asymmetric dimethyl-arginine and homocysteine in the interplay between arginine and NO metabolism, 4) to develop and apply a new mass isotopomer method for determination of albumin synthesis rate and then to adapt this method to assess the synthesis rates of acute phase proteins, including CRP, fibronectin, Apo B 100 and other liver export proteins, at different stages of recovery in burn patients. This research is expected to significantly expand our understanding of the pathophysiology of the N catabolism and how it might be through "designer" nutritional / pharmacological therapy.

能量和氨基酸代谢调节的改变在病因学上具有重要意义， 烧伤病人的发病率和死亡率。该项目涉及体内的综合研究， 所谓的“条件性不可缺少的”氨基酸的代谢的改变，特别是 谷氨酸-谷氨酰胺、精氨酸和含硫氨基酸。具体目标是：1）评估谷氨酰胺代谢的状态，与其在葡萄糖和能量底物代谢以及维持氮（N）经济中的作用有关。这一目标将涉及烧伤患者和健康对照受试者的研究，旨在评估肠内和肠外谷氨酰胺补充对内脏蛋白和氨基酸代谢的影响。在烧伤兔模型中的研究将包括使用高血氨钳夹和质谱法，以评估谷氨酰胺在碳和氮代谢途径中的主要命运。2)探讨烧伤病人的营养状况及影响谷胱甘肽（GSH）代谢的营养因素，尤其是含硫氨基酸。这一目标将包括对患者的研究和对烧伤动物模型的一系列调查。我们将确定谷胱甘肽合成的条件不可缺少的氨基酸前体（谷氨酸/谷氨酰胺，甘氨酸和半胱氨酸）在烧伤后谷胱甘肽代谢的调节中的作用。3)探讨烧伤后精氨酸代谢状况及NO合成的调控因素与器官功能（精氨酸供应的影响及不同器官，尤其是肺、肝、肾NO合成的代谢调节）的关系。这一目标将包括初步确定不对称二甲基精氨酸和同型半胱氨酸的意义， 精氨酸与NO代谢的相互作用; 4）建立一种新的测定白蛋白合成速率的质量同位素方法，并应用于烧伤患者不同恢复期急性期蛋白（包括CRP、纤连蛋白、载脂蛋白B 100等）的合成速率的测定。这项研究预计将显着扩大我们的N catastrophic的病理生理学的理解，以及它可能是如何通过“设计师”的营养/药理学治疗。