GENETIC EFFECTS ON FOLATE-DEPENDENT ONE-CARBON METABOLISM PROTOCOL 2

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。健康营养充足的人类受试者（20-30岁）将被纳入，并将接受多达5次稳定同位素输注。至少5名受试者必须完成研究。基本的饮食和输液程序将以本项目先前进行的程序为基础。前三次输注将分别给药[3-13C]丝氨酸、[13C]甘氨酸或[U-13C]蛋氨酸，以比较这些化合物作为碳供体的情况。受试者还将被注入氘标记的丝氨酸（[2H3]丝氨酸），这将允许计算丝氨酸加工过程中细胞质和线粒体途径对碳单元生成的相对贡献。每个输注液还将含有[2H3]亮氨酸作为对照，以评估蛋白质周转引起的氨基酸通量。这些研究产生的数据将有助于评估影响人体代谢的营养和遗传变量的后果，并将有助于设计未来的研究

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. Healthy adequately nourished human subjects (20-30 yr) will be enrolled, and will receive up to 5 stable isotopic infusions. At least 5 enrolled subjects must complete the study. The basic dietary and infusion procedures will be based on those conducted previously in this project. The first three infusions will involve individual administration of [3-13C] serine, [13C] glycine or [U-13C] methionine to compare these compounds as carbon donors. The subjects also will be infused with deuterium-labeled serine ([2H3] serine), which will allow calculation of the relative contributions of cytosolic and mitochondrial pathways of serine processing for generation of carbon units. Each infusion solution will also contain [2H3] leucine as a control to assess amino acid flux due to protein turnover. The data arising from these studies will aid in assessing the consequences of nutritional and genetic variables affecting human metabolism and will aid in the design of future studies