Investigations into the Glutamine-Citruline-Arginine Pathway in Sepsis

脓毒症中谷氨酰胺-瓜氨酸-精氨酸途径的研究

• 批准号: 7707290
• 负责人: Christina C. Kao
• 金额: $ 17.32万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7707290
• 关键词: Age; Amino Acids; Ammonia; Antioxidants; Appearance; Arginine; Blood Pressure; Blood Vessels; Carbon; Cell Proliferation; Cells; Child Nutrition; Citrulline; Clinical; Critical Care; Critical Illness; Dipeptides; Drug Metabolic Detoxication; Enrollment; Enteral; Enterocytes; Gender; Gluconeogenesis; Glucose; Glutamates; Glutamine; Glutathione; Goals; Health; Immunologics; Infection; Injury; Intensive Care Units; Intestines; Intravenous; Investigation; Kidney; Knowledge; Lead; Leucine; Link; Liver; Lung; Lung diseases; Lymphocyte; Maintenance; Medical center; Medicine; Metabolic; Metabolic Pathway; Metabolism; Methods; Morbidity - disease rate; Multi-Hospital Systems; Nitric Oxide; Nitrogen; Non-Essential Amino Acid; Nucleic Acids; Nutritional Study; Nutritional Support; Organ; Pathway interactions; Patients; Peripheral; Physiological; Plasma; Play; Principal Investigator; Production; Protein Biosynthesis; Proteins; Proteolysis; Purines; Pyrimidine; Pyrimidines; Recovery; Regulation; Reporting; Research; Research Personnel; Resources; Role; Scientist; Sepsis; Sleep; Stress; Supplementation; Testing; Texas; Tissues; Tracer; Training Programs; cell growth; college; fighting; immune function; improved; indexing; macrophage; mortality; professor; protein metabolism; public health relevance; purine; randomized placebo controlled trial; research study; response; septic; skills; stable isotope; uptake

DESCRIPTION (provided by applicant): Dr. Christina Kao is an assistant professor in the Section of Pulmonary, Critical Care, and Sleep Medicine at Baylor College of Medicine (BCM). Her short-term goal is to develop the knowledge and skills to conduct metabolic research using stable isotope methods. Her long-term goal is to become an independent investigator studying nutritional and metabolic aspects of critical illness and lung disease. Dr. Kao is enrolled in the MS track of the Clinical Scientist Training Program at BCM, and she has access to the extensive resources of the Texas Medical Center, including the Children's Nutrition Research Center and a multi-hospital system. Dr. Kao will examine the metabolic relationship between glutamine and arginine. These amino acids are linked by an inter-organ pathway involving intestinal conversion of glutamine to citrulline followed by renal uptake of citrulline and conversion to arginine. She proposes that, in septic patients, (a) alterations in the availability and whole-body and splanchnic metabolism of glutamine will lead to decreased synthesis of citrulline and arginine and (b) glutamine supplementation will elicit an increase in citrulline, and hence arginine, synthesis. Stable isotope tracer methods will be used to test specific aspects of these hypotheses. Specific aim 1 will determine differences in the rate of glutamine conversion to citrulline and the fractional splanchnic extraction of glutamine in septic patients and healthy controls. The hypothesis is that septic patients have decreased citrulline synthesis from glutamine, and that the rate of citrulline production is directly related to the rate of splanchnic extraction of glutamine. Specific aim 2 will determine the rate of de novo arginine synthesis from its precursors, citrulline and glutamine, in septic patients and healthy controls. The hypothesis is that decreased glutamine availability leads to decreased de novo arginine synthesis in septic patients. Specific aim 3 will determine the effects of enteral and parenteral glutamine supplementation on arginine and citrulline synthesis in septic patients. The hypothesis is that glutamine supplementation of septic patients will lead to increased citrulline and de novo arginine synthesis, and the magnitude of this increase will be greater with enteral compared to parenteral supplementation. PUBLIC HEALTH RELEVANCE: Two compounds, arginine and glutamine, help our body fight severe infections. This research will help to better define the relationship between these two compounds and will determine if supplying more of one (glutamine) will in turn lead to increases in the other (arginine). Better understanding of the body's utilization of these two compounds can contribute to improved nutritional therapy in patients with severe infection.

描述（由申请人提供）： Christina Kao博士是贝勒医学院（BCM）的肺部，重症监护和睡眠医学部门的助理教授。她的短期目标是发展知识和技能，使用稳定的同位素方法进行代谢研究。她的长期目标是成为一名独立研究者，研究危害疾病和肺部疾病的营养和代谢方面。 Kao博士在BCM参加了临床科学家培训计划的MS轨道，她可以使用得克萨斯州医疗中心的广泛资源，包括儿童营养研究中心和多医院系统。 Kao博士将检查谷氨酰胺和精氨酸之间的代谢关系。这些氨基酸通过涉及谷氨酰胺到瓜氨酸的肠道转化，然后肾脏摄取瓜氨酸和转化为精氨酸的肠间途径。她建议，在化粪池患者中，（a）谷氨酰胺的可用性以及全身和斑点代谢的改变将导致瓜氨酸和精氨酸的合成降低，以及（b）补充谷氨酰胺会导致瓜氨酸的增加，因此，精氨酸，因此，合成。稳定的同位素示踪剂方法将用于测试这些假设的特定方面。具体的目标1将确定谷氨酸转化为瓜氨酸的速率和脓毒症患者和健康对照组中谷氨酰胺的分数提取的差异。假设是化粪池患者从谷氨酰胺中降低了瓜氨酸的合成，而瓜氨酸的生产速率与谷氨酰胺的诊断提取率直接相关。具体的目标2将在化粪池患者和健康对照组中从其前体，瓜氨酸和谷氨酰胺的前体，瓜氨酸和谷氨酰胺的合成速率。假设是，谷氨酰胺的可利用率降低会导致化粪池患者的新精氨酸合成降低。具体目标3将确定肠内肠内和肠胃外谷氨酰胺对化脓性患者精氨酸和瓜氨酸合成的影响。假设是，败血症患者补充谷氨酰胺将导致瓜氨酸和新精氨酸的合成增加，并且与肠胃外补充相比，肠内增加的幅度将更大。 公共卫生相关性：两种化合物，精氨酸和谷氨酰胺，有助于我们的身体对抗严重的感染。这项研究将有助于更好地定义这两种化合物之间的关系，并确定提供更多的一种（谷氨酰胺）是否会导致另一种（精氨酸）的增加。更好地了解人体对这两种化合物的利用，可以改善严重感染患者的营养疗法。