NUTRITIONAL AND FUNCTIONAL METHIONNE REQUIREMENTS IN SEPTIC ADOLESCENTS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 本研究是我们对重症败血症儿童硫氨基酸代谢研究的继续。该项目的近期目标是更好地确定从新生儿到青少年的健康人和重症败血症儿科人群的含硫氨基酸需求。这是一个雄心勃勃的目标，每次只能通过一个项目来实现。在这项提案中，我们只关注健康和危重的青少年人口。健康儿童对氨基酸的需求基于极其有限的数据。在营养和功能平衡的温度下，危重儿童的氨基酸需求尚不清楚。蛋氨酸是一种不可或缺的含硫氨基酸，除了DNA甲基化和肌酸、胆碱等重要化合物的生物合成外，还可用于蛋白质合成。然而，过量的蛋氨酸摄入可能通过过量产生同型半胱氨酸而导致危重疾病的内皮功能障碍。在目前的研究中，我们建议确定蛋氨酸的营养需求，并开始探索196名重症败血症青少年和196名健康青少年在5年内的功能需求。我们建议修改氨基酸需要量测定的“金”标准技术--24小时指示氨基酸氧化和平衡技术，使其适用于健康和危重人群。我们还计划将蛋氨酸摄入量与疾病严重程度、内皮功能障碍的标志物和外周淋巴细胞DNA甲基化的比率联系起来。我们的长期目标是最终确定维持从新生儿到青少年的儿科人群的营养平衡和功能的氨基酸需求，改善患病人群的结局，并在健康的儿科人群中基于定量、可靠的数据建立健全的营养标准。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This portocol is a continuation of our studies on sulfur amino acid metabolism in critically ill septic children. The immediate objectives of this project are to better define sulfur amino acid requirements in the healthy and in the critically ill septic pediatric population from newborn to adolescent. This is an ambitious goal that can only be approached with one project at a time. In this proposal we are focused exclusively in the healthy and critically ill adolescent population. Amino acid requirements in healthy children are based on extremely limited data. The amino acid requirements for critically ill children in therms of nutritional and functional balance are not known. Methionine, an indispensable sulfur amino acid serves for protein synthesis in addition to DNA methylation and biosynthesis of important compounds such as creatine, choline, etc. However, an excessive methionine administration may contribute to endothelial dysfunction of critical illness through an excessive production of homocysteine. In the present studies we propose to define nutritional requirements of methionine and to begin to explore functional requirements in 196 critically ill septic adolescents and 196 healthy adolescents over a period of 5 years. We propose to modify the "gold" standard techniqure of amino acid requirement determination, the 24h-indicator amino acid oxidation and balance technique, to make it applicable to both, the healthy and critically ill populations. We plan also to correlate methionine intake with severity of disease, markers of endothelial dysfunction and rates of DNA methylation in peripheral lymphocytes. Our long-term aim is to eventually determine the amino acid requirements that will maintain nutritional balance and function in the pediatric population from newborn to adolescents, to improve outcome in the sick population and to establish sound nutritional standards based on quantitative, reliable data in the healthy pediatric population.