FETAL BRANCHED-CHAIN AMINO ACID AND KETO-ACID METABOLISM

胎儿蛋白质合成和氨基酸代谢的调节是 对了解胎儿正常或异常生长至关重要。 最好用同位素示踪剂进行调查， 示踪剂的稀释被用作生产、利用 和示踪氨基酸的氧化。 在项目期间，工作 将继续胎儿亮氨酸动力学模型，利用输注 ~（13）C-~（15）N-亮氨酸进入胎儿室及亮氨酸的测定 碳氮动力学 胎儿亮氨酸动力学的调节将是 在正常血糖和高血糖钳夹研究中探索，而胰岛素 浓度维持在正常范围内，以及在急性 低胰岛素血症和高胰岛素血症的内皮细胞。 还将开始进行研究，以制定和验证一个三个部分 胎儿、子宫胎盘和母体亮氨酸动力学模型 怀孕母羊 虽然同位素建模很复杂，但分析 该模型的方法目前正在我们的 实验室 该模型最终将用于检验假设 关于母体蛋白质和氮的变化 动力学影响胎儿生长和氮平衡。 最后，我将花一些时间在实验室里， 在同位素建模和质量领域的专家 光谱测定分析法. 目前，罗伯特·沃尔夫博士和约翰· 海耶斯已同意提供培训和指导，在各自的 实验室为期一至三个月。 我相信这些 休假将是非常宝贵的，在促进我的能力，设计和应用 哺乳动物胎儿生长问题的示踪方法。

The regulation of fetal protein synthesis and amino acid catabolism is central to an understanding of fetal growth, normal or aberrant. Investigations are best conducted with isotopic tracers, whereby the dilution of the tracer is used as an estimate of production, utilization and oxidation of the tracer amino acid. During the proposed project, work will continue on the model of fetal leucine kinetics, utilizing infusion of 1-13C-15N-leucine into the fetal compartment and determination of leucine carbon and nitrogen kinetics. Regulation of fetal leucine kinetics will be explored during euglycemic and hyperglycemic clamp studies, while insulin concentrations are maintained in the normal range, as well as during acute hypo- and hyperinsulinemic euglycemia. Studies will also be begun to develop and validate a three compartment fetal, uteroplacental and maternal model of leucine kinetics in the pregnant ewe. While the isotopic modeling is complex, the analytical methodology for this model is all presently being performed in our laboratory. This model will be ultimately utilized to test hypotheses regarding the manner in which alterations in maternal protein and nitrogen kinetics affect fetal growth and nitrogen balance. Finally, I will be spending periods of time in the laboratories of established experts in the fields of isotope modeling and mass spectrometric analysis. At the present time, Drs. Robert Wolfe and John Hayes have agreed to provide training and guidance in their respective laboratories for periods of one to three months. I am confident these sabbaticals will be invaluable in furthering my ability to design and apply tracer methodology to problems of mammalian fetal growth.