FETAL BRANCHED CHAIN AMINO ACID AND KETO-ACID METABOLISM

胎儿蛋白质合成和氨基酸分解代谢的调节是 是了解胎儿发育的核心，无论是正常的还是异常的。 最好使用同位素示踪剂进行调查，这样 示踪剂的稀释度被用来估计产量、利用率 和示踪氨基酸的氧化。在提议的项目期间，工作 将继续研究胎儿亮氨酸动力学模型，利用输注 1-13C-15N-亮氨酸进入胎儿房室及亮氨酸的测定 碳和氮的动力学。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期间进行探索，而胰岛素 浓度维持在正常范围内，以及在急性 低胰岛素和高胰岛素正常血糖。 还将开始研究开发和验证三个隔间 胎儿、子宫胎盘和母体亮氨酸动力学模型 怀孕的母羊。虽然同位素模型很复杂，但分析 此模型的方法论目前都在我们的 实验室。这个模型最终将被用来检验假说。 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，我将花一段时间在 在同位素建模和质量领域有经验的专家 光谱分析。目前，罗伯特·沃尔夫博士和约翰博士 海耶斯已同意在各自的培训和指导中 实验室为期一至三个月。我对这些很有信心 休假对提高我的设计和应用能力将是无价的。 哺乳动物胎儿生长问题的示踪方法学。

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.