KINETICS OF FETAL LEUCINE AND KETOISOCAPROATE METABOLISM

胎儿的正常生长对出生后的生长发育至关重要。 胎儿 代谢，特别是能量需求和胎儿蛋白 代谢与子宫内生长直接相关。 整体 本提案的目的是提高我们对蛋白质的理解 通过评估胎儿在宫内生活期间的代谢 定量氨基酸代谢的动力学和表征 母亲代谢变化对胎儿这些指标的影响 新陈代谢. 代表性必需氨基酸亮氨酸的内源通量 酸以及其酮酸酮异己酸（KIC）的通量率 亮氨酸碳氧化的速率将使用双波长荧光法测定。 同位素稀释技术在羊胎儿长期导尿中的应用 模型 氨基酸代谢的这些动态定量方面将被用作 内源性胎儿蛋白代谢的动力学指标，以探索 影响： A.母亲禁食，因为母亲禁食和营养不良是 与胎儿发育迟缓有关 B。亮氨酸输注到母亲，因为亮氨酸已被证明发挥了 在体外和体内对蛋白质代谢的调节作用， 对母体蛋白质代谢影响可能影响胎儿氨基酸 代谢和随后的宫内生长。 C.正常妊娠期间胎儿高胰岛素血症与不良妊娠期间胎儿高胰岛素血症一样 控制母亲糖尿病，这是与胎儿 胎儿的过度生长和代谢变化， 宫内和即刻的发病率和死亡率增加 产后生活 D.严格控制糖尿病期间发生的母体低血糖 母亲的糖尿病。 这项研究将加强我们对胎儿蛋白质代谢的理解， 影响这种新陈代谢的因素，并可能为我们提供方法 在宫内生活期间和之后的治疗干预。

Normal fetal growth is critical to postnatal growth and development. Fetal metabolism and, in particular, energy requirements and fetal protein metabolism are directly associated with intrauterine growth. The overall objective of this proposal is to enhance our understanding of protein metabolism in the fetus during intrauterine life by assessing quantitatively the kinetics of amino acid metabolism and by characterizing the effect of metabolic changes in the mother on these indices of fetal metabolism. The endogenous flux rates of leucine as a representative essential amino acid as well as the flux rates of its ketoacid ketoisocaproic acid (KIC) and the rates of leucine carbon oxidation will be determined using a double isotope dilution technique in the chronically catheterized ovine fetus model. These dynamic quantitative aspects of amino acid metabolism will be used as kinetic indices of endogenous fetal protein metabolism in order to explore the effect of: A. Maternal fasting since fasting and undernutrition in the mother are associated with fetal growth retardation. B. Leucine infusion to the mother since leucine has been shown to play a regulatory role on protein metabolism in vitro and in vivo and therefore its effect on maternal protein metabolism may influence fetal amino acid metabolism and subsequently intrauterine growth. C. Fetal hyperinsulinemia during euglycemia as it occurs during poor control of maternal diabetes mellitus, which is associated with fetal overgrowth and metabolic changes in the fetus that are responsible for increased morbidity and mortality during intrauterine and immediate postnatal life. D. Maternal hypoglycemia as it occurs during strict control of diabetes mellitus in the mother. This study will enhance our understanding of fetal protein metabolism and the factors affecting this metabolism and possibly provide us with methods of therapeutic intervention during and following intrauterine life.