KINETICS OF FETAL LEUCINE AND KETOISOCAPROATE METABOLISM

正常的胎儿生长发育对出生后的生长发育至关重要。胎儿 新陈代谢，特别是能量需求和胎儿蛋白质 新陈代谢与胎儿宫内发育直接相关。整体而言 这项建议的目的是增进我们对蛋白质的了解 胎儿在宫内生命中的代谢 氨基酸代谢动力学的定量和表征 母体代谢变化对胎儿上述指标的影响 新陈代谢。 亮氨酸作为代表必需氨基酸的内源通透率 酸及其酮酸酮基异己酸(KIC)的通量速率 而亮氨酸碳氧化的速率将用双倍 绵羊胎儿慢性插管后的同位素稀释技术 模特。 氨基酸代谢的这些动态定量方面将被用作 内源性胎儿蛋白质代谢动力学指标的探讨 以下因素的影响： 答：母亲禁食和母亲营养不良是 与胎儿发育迟缓有关。 B.给母亲注射亮氨酸，因为亮氨酸已经被证明起到了 在体内外对蛋白质代谢的调节作用 其对母体蛋白质代谢的影响可能影响胎儿氨基酸 新陈代谢和随后的宫内生长。 C.正常血糖期间的胎儿高胰岛素血症，因为它发生在贫穷时期 控制母体糖尿病，这与胎儿 胎儿的过度生长和代谢变化是导致 宫内和即刻的发病率和死亡率增加 出生后的生活。 D.在严格控制糖尿病期间发生的母亲低血糖 母亲患上了糖尿病。 这项研究将加深我们对胎儿蛋白质代谢和 影响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.