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

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。将招募营养充足的健康人类受试者（20-30岁），并将接受最多5次稳定同位素输注。至少5例入组受试者必须完成研究。基本的饮食和输液程序将基于本项目之前进行的程序。前三次输注将涉及[3- 13 C]丝氨酸、[13 C]甘氨酸或[U-13 C]甲硫氨酸的单独给药，以比较这些化合物作为碳供体。受试者还将输注氘标记的丝氨酸（[2 H3]丝氨酸），这将允许计算丝氨酸加工的细胞溶质和线粒体途径对碳单元生成的相对贡献。每种输注溶液还将含有[2 H3]亮氨酸作为对照，以评估由于蛋白质周转引起的氨基酸通量。从这些研究中获得的数据将有助于评估影响人体新陈代谢的营养和遗传变量的后果，并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