DIETARY METHIONINE UPTAKE BY SPLANCHNIC REGION IN HEALTHY AND SICK CHILDREN

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。 内脏区域在全身氨基酸代谢的动态平衡中起着重要作用，并选择性地影响随后被释放到体循环中的氨基酸吸收模式。在危重疾病期间，内脏区域会受到严重影响，并可能影响氨基酸代谢。关于器官间氨基酸交换以及内脏摄取和分解代谢氨基酸在危重病患者中的作用的数据有限。为了确定肠外和肠内氨基酸的需要量，有必要确定内脏区域氨基酸第一次消失的程度。我们计划研究一组健康的青少年，他们将作为我们重症青少年组的对照。 硫磺氨基酸在健康青少年中的内脏摄取还没有确定，需要定义。因此，需要确定患病儿童对含硫氨基酸的肠道需要量。 该方案的第一个目标是研究健康儿童和青少年对蛋氨酸和半胱氨酸内脏的摄取。对健康儿童的研究将为我们的危重人口提供控制。我们正在请求GCRC的支持，以便在健康的儿童中进行研究。 我们的目标是在第一组研究中进行预先持续的静脉和肠道注射L-[1-13C]和L[2H2]蛋氨酸，在第二组研究中进行L-[1-13C]和L[2H2]半胱氨酸的注射，并使用这些数据来评估内脏隔离对蛋氨酸和半胱氨酸需求的贡献。 初级终点：甲硫氨酸或半胱氨酸示踪剂在第一次通过内脏区域时消失的部分。 该方案是我们对患病儿童硫氨基酸代谢研究的继续。我们已经进行了危重婴儿、儿童和青少年内脏蛋氨酸摄取的研究(请参阅初步数据)。 内脏区域在全身氨基酸代谢的动态平衡中起着重要作用。内脏区域选择性地影响被吸收的氨基酸的模式，这些氨基酸随后被释放到体循环中。肠道氨基酸代谢在调节摄入的氨基酸进入门静脉循环中起着重要作用。因此，饮食中的氨基酸模式与门静脉血中的氨基酸模式明显不同，并不反映它们对肠外组织的可用性。这一概念对蛋白质和氨基酸营养具有重要意义。食物中必需氨基酸的广泛分解代谢首先通过小肠，这是人体的一个大器官，导致营养效率降低。因此，肠道氨基酸代谢会影响日粮氨基酸的利用效率，从而影响其需要量。此外，目前尚不清楚器官间氨基酸交换和内脏摄取在病理条件下如何受到影响，以及这些过程在疾病条件下如何影响氨基酸需求。 有关于健康受试者内脏对亮氨酸、精氨酸、谷氨酰胺和蛋氨酸摄取的数据。在儿科人群中，有两项关于内脏亮氨酸摄取的研究，一是囊性纤维化患者的研究，二是新生儿期的研究。这些研究产生的亮氨酸内脏摄取值分别为24%和30%。没有关于健康或患病儿童的蛋氨酸和半胱氨酸内脏摄取的数据。因此，这项建议的第一个目标是确定患病儿童内脏对蛋氨酸和半胱氨酸的摄取率。

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. The splanchnic region plays a significant role in the homeostasis of whole body amino acid metabolism and selectively influences the pattern of absorbed amino acids that is subsequently released into the systemic circulation. During critical illness the splanchnic area is profoundly affected, and may influence amino acid metabolism. There are limited data on inter-organ amino acid exchange and the role of splanchnic uptake and catabolism of amino acids in critically ill patients. To determine parenteral and enteral amino acid requirements, it is necessary to determine the extent of the first pass disappearance of amino acids in the splanchnic region. We plan to study a group of healthy adolescents who will serve as controls for our critically ill adolescent group. Sulfur amino acid splanchnic uptake in healthy adolescents has not been determined and needs to be define. Hence enteral requirement of sulfur amino acids in sick children need to be defined. The first objective of this protocol is to conduct studies of methionine and cysteine splanchnic uptake in healthy children adolescents. The studies in healthy children will serve as controls for our critically ill population. We are requesting GCRC support to conduct our studies in the healthy children. We aim to conduct primed, constant simultaneous intravenous and enteral infusions of L-[1-13C] and L[2H2 ]methionine in a first set of studies and of L-[1-13C] and L[2H2 ] cysteine in a second set of studies in healthy children and to use these data to estimate the contribution of splanchnic sequestration to methionine and cysteine requirements. Primary Endpoint: The fraction of methionine or cysteine tracer that disappears in a first-pass through the splanchnic area This protocol is a continuation of our studies on sulfur amino acid metabolism in sick children. We have already conducted studies of methionine splanchnic uptake in critically ill infants, children and adolescents (Please see preliminary data). The splanchnic region plays a significant role in the homeostasis of whole body amino acid metabolism. The splanchnic area selectively influences the pattern of absorbed amino acids that is subsequently released into the systemic circulation. Intestinal amino acid metabolism plays an important role in modulating the entry of absorbed dietary amino acids into the portal circulation. Thus, the pattern of amino acids in the diet differs markedly from that in portal venous blood and does not reflect their availability to extraintestinal tissues. This concept has important implications for protein and amino acid nutrition. The extensive catabolism of dietary essential amino acids in the first pass by the small intestine, a large organ in the body, results in decreased nutritional efficiency. Thus, intestinal amino acid metabolism will influence the utilization efficiency of dietary amino acids and therefore their requirements. Furthermore, it is not known how inter-organ amino acid exchange and splanchnic uptake are affected under pathologic conditions, and how these processes influence amino acid requirements under conditions of disease. There are data on the splanchnic uptake of leucine, arginine, glutamine and methionine in healthy subjects. In the pediatric population there are two studies on leucine splanchnic uptake, in a population of patients with cystic fibrosis and in the newborn period. These studies yield leucine splanchnic uptake values of 24% and 30% respectively. There are no data on methionine and cysteine splanchnic uptake in healthy or sick children. Therefore, the first objective of this proposal is to determine the rates of splanchnic uptake of methionine and cysteine in sick children.