PROTEIN/ENERGY DEMANDS OF SICKLE CELL DISEASE

纯合镰状细胞病(HbSS)是一个主要的健康问题。 在整个美国和世界范围内导致血管- 闭塞事件，各种继发性疾病并发症，以及 预期寿命的缩短。HBSS是一种遗传性疾病，其特征是 由取代的红细胞(RBC)引起的镰刀状 谷氨酸与Valine在β链上的第6位 血红蛋白。由于这种结构变化， 红细胞从正常的120天大大减少到大约 10天。红细胞的镰刀状会导致慢性贫血和 增加红细胞分解代谢和合成。这些生理上的 微扰有可能促进能量的增加 支出，增加蛋白质分解和合成，增加 无氧代谢，并改变胰岛素的作用。这其中的每一个 代谢紊乱能够改变特定的底物 氧化和增加蛋白质和能量的需求。整体而言 拟议研究的目的是确定HbSS对以下方面的影响 全身和骨骼肌营养代谢和需求。 已经设计了两个独立的协议来识别 蛋白质和能量需求增加的机制 在Hbss期间。这些方案将1)定义营养物质的变化 HbSS期间的代谢从基础和期间改变能量代谢 食物的模拟摄入量，2)决定是否增加 蛋白质和/或能量的供应改善了蛋白质的动态平衡 HBSS患者3)确定蛋白质合成需求如何 红细胞和其他特定组织对蛋白质和能量产生影响 HbSS中的要求，以及4)定义HbSS对 胰岛素介导的营养利用。因此，协议将 重点关注与摄取后、与进食有关的事件和 胰岛素介导的代谢。这些实验将使用同位素 示踪技术，间接量热法，营养输注，以及 糖化血红蛋白综合征患者的正常血糖-高胰岛素钳夹。什么时候 结合起来，建议的协议将增强我们对 HbSS如何改变蛋白质和能量代谢，并将识别 这些变化的机制。糖化血红蛋白对健康的贡献 护理费用很高，从这些研究中获得的知识 将使我们更好地了解各种新陈代谢过程 与HbSS相关联。这些知识将有助于设计 适当的营养养生，从而最终得到更好的 疾病后果。

Homozygous sickle cell disease (HbSS) is a major health problem throughout the United States and the world that results in vaso- occlusive events, a variety of secondary disease complications, and a reduced life expectancy. HbSS is a genetic disorder Characterized by the sickling of red blood cells (RBC) due to the replacement of glutamic acid with valine in position 6 on the beta chains of hemoglobin. As a result of this structural change, the life span of the RBC is greatly reduced from the normal 120 days to approximately 10 days. The sickling of RBCs leads to a chronic anemia and increased RBC catabolism and synthesis. These physiological perturbations have the potential to promote increased energy expenditure, increased protein breakdown and synthesis, increased anaerobic metabolism, and altered insulin action. Each of these metabolic derangements is capable of altering specific substrate oxidation and increasing protein and energy demands. The overall aim of the proposed research is to determine the impact of HbSS on whole-body and skeletal muscle nutrient metabolism and demands. Two separate protocols have been designed to identify the mechanisms by which protein and energy demands are increased during HbSS. These protocols will 1) define how changes in nutrient metabolism during HbSS alter energy metabolism basally and during the simulated ingestion of a meal, 2) determine whether increased protein and/or energy availability improves protein homeostasis in HbSS patients 3) identify how the protein synthetic demands of RBCs and other specific tissues impact upon the protein and energy requirements in HbSS, and 4) define the influence of HbSS on insulin-mediated nutrient utilization. Therefore, the protocols will focus on events associated with post-absorptive, meal-related, and insulin-mediated metabolism. These experiments will use isotopic tracer techniques, indirect calorimetry, nutrient infusions, and euglycemic-hyperinsulinemic clamps in HbSS patients. When combined, the proposed protocols will enhance our understanding of how HbSS alters protein and energy metabolism and will identify mechanisms for these alterations. The contribution of HbSS to health care costs is significant, and the knowledge gained from these studies will enable us to better understand the various metabolic processes associated with HbSS. This knowledge will assist in the design of appropriate nutritional regimens, thereby culminating in better disease outcomes.