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

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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