Parenteral Methionine Requirements in Septic Children

脓毒症儿童的肠外蛋氨酸需求

• 批准号: 8274581
• 负责人: Leticia Castillo
• 金额: $ 34.56万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-06-01 至 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8274581
• 关键词: Acute; Age; Amino Acids; Antioxidants; Betaine; Cerebral Edema; Child; Childhood; Cholestasis; Choline; Chronic; Clinical; Clinical Research; Creatine; Critical Illness; Cysteine; DNA Methylation; Data; Dietary Intervention; Dietary intake; Dose; Enteral; Enteral Feeding; Equilibrium; Essential Amino Acids; Event; Figs - dietary; Folate; Future; Glutathione; Hepatic; Homocysteine; Homocystine; Human; Inflammation; Inflammatory; Intake; Life; Metabolism; Methionine; Methionine Metabolism Pathway; Morbidity - disease rate; Non-Essential Amino Acid; Nutritional; Nutritional Requirements; Nutritional Support; Outcome; Oxidation-Reduction; Parenteral Nutrition; Pathway interactions; Patients; Pediatric Intensive Care Units; Policies; Polyamines; Process; Production; Protein Biosynthesis; Proteins; Publishing; Reaction; Recommendation; Role; Seizures; Sepsis; Signal Transduction; Skeletal Muscle; Sulfur; Sulfur Amino Acids; Techniques; Testing; Total Parenteral Nutrition; Toxic effect; Transduction Gene; base; clinically relevant; cysteinylglycine; evidence base; functional outcomes; high risk; methyl group; mortality; oxidation; response; septic; sound; transmethylation

DESCRIPTION (provided by applicant): Total Parenteral nutrition (TPN) is life-saving for children unable to tolerate enteral feedings. A large proportion of critically ill pediatric ICU patients are children with chronic conditions suffering from an acute episode of sepsis, many of these patients require extended use of TPN. Morbidity and mortality is higher in these patients. The sulfur amino acids methionine and cysteine are important in critical illness due to methionine role as a methyl group donor for creatine, choline and DNA methylation, and as the precursor of cysteine, the rate limiting amino acid in glutathione (GSH) synthesis, which is a major antioxidant. Parenteral sulfur amino acid requirements in critically ill septic children are not known, but currently children receive amino acid formulas greatly supplemented with methionine and devoid or supplying minimal amount of cysteine. This application will determine the parenteral requirements of methionine, in the presence of cysteine, in critically ill septic patients requiring extended use of TPN (aim # 1), by using the indicator amino acid oxidation and balance technique (IAAOB). This is a dose-response technique. The endpoint is methionine requirement as determined by the breakpoint between graded levels of parenteral methionine intake and the rates of oxidation and balance of an indicator amino acid. We hypothesize that the current parenteral amino acid formulas devoid or providing minimal amounts of cysteine, but largely supplemented with methionine, provide methionine largely in excess of requirements, and that parenteral methionine requirements should be defined. Dietary intake drives metabolism. Hence in aim # 2 we will explore methionine metabolism through the rates of transmethylation, transsulfuration and remethylation at the current standard intakes of methionine of 120 mg.kg.d with negligible amounts of cysteine, provided by commercial amino acid formulas, versus the sulfur amino acid intake defined in aim # 1. The endpoint is the rates of transmethylation, remethylation and transsulfuration at the two different levels of parenteral sulfur amino acid intakes, GSH synthesis rates and methyl group availability defined by the adenosyl- methionine/adenosyl-homocysteine ratio. We hypothesize that under conditions of inflammation a balanced sulfur amino acid intake, involving parenteral methionine and cysteine, is required to maintain optimal sulfur amino acid metabolism and function. Exclusive supply of methionine or a limited amount of cysteine will fail to support sulfur amino acid function. In summary, our overall objective is to generate data to support changes on nutritional policy on parenteral sulfur amino acid intakes, and in the future test the impact of our established requirements on clinically relevant outcomes.

描述（由申请人提供）：总肠胃外营养（TPN）为无法忍受肠内喂养的儿童挽救生命。大部分患病的儿科ICU患者是患有急性败血症的慢性疾病的儿童，其中许多患者需要扩展使用TPN。这些患者的发病率和死亡率更高。硫氨基酸蛋氨酸和半胱氨酸在危害疾病中很重要，这是由于蛋氨酸作为肌酸，胆碱，胆碱和DNA甲基化的甲基供体的作用，并且是半胱氨酸的前体，谷胱甘肽（GSH）合成的速率限制了氨基酸，这是主要的抗氧化剂。肠胃外硫氨基酸的需求尚不清楚，但目前儿童接受氨基酸配方，大量补充了蛋氨酸和无脱酮或供应最少的半胱氨酸。该应用将通过使用指标氨基酸氧化和平衡技术（IAAOB）来确定蛋氨酸在半胱氨酸的存在下甲硫氨酸的肠胃外需求（AIM＃1）。这是一种剂量反应技术。终点是蛋氨酸的需求，取决于肠胃蛋白摄入的分级水平与指示氨基酸的氧化和平衡速率的断点。我们假设当前的肠胃外氨基酸配方无孔或提供最少的半胱氨酸，但在很大程度上补充了蛋氨酸，在很大程度上提供了蛋氨酸的要求，并且应定义肠胃丙氨酸的需求。饮食摄入驱动新陈代谢。因此，在目标＃2中，我们将通过当前的蛋氨酸标准摄入量的跨甲基化，转硫和替代甲基化的速率探索蛋氨酸的代谢，并以120 mg.kg.d的标准摄入量，其半胱氨酸含量可忽略不计，该含量可忽略不计，由商业氨基酸公式，与硫酸氨基酸的含量为硫酸氨基酸的速率和硫酸氨基酸的速率为1点，并在AIM中进行了sapy的速率。在两个不同水平的肠胃硫氨基酸摄入量，GSH合成速率和甲基甲基的可用性下，由腺苷蛋氨酸/腺苷同型半胱氨酸比率定义的甲基含量。我们假设在炎症条件下，需要平衡的硫氨基酸摄入，涉及肠胃蛋白和半胱氨酸需要维持最佳的最佳硫氨基酸代谢和功能。蛋氨酸或有限量的半胱氨酸的独家供应将无法支持硫氨基酸功能。总而言之，我们的总体目标是生成数据，以支持肠胃外硫氨基酸摄入的营养政策的变化，并在将来测试我们既定要求对临床相关结果的影响。