PROTEIN/ENERGY DEMANDS OF SICKLE CELL DISEASE

纯合子镰状细胞病（HbSS）是一个主要的健康问题 在美国和世界各地，这导致血管- 闭塞事件、各种继发性疾病并发症，以及 预期寿命缩短。HbSS是一种遗传性疾病， 红细胞（RBC）的镰状化是由于 谷氨酸与缬氨酸的β链上的位置6 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天红细胞的镰状化导致慢性贫血， 增加红细胞催化剂和合成。这些生理 扰动有可能促进能量的增加 增加蛋白质的分解和合成， 无氧代谢和胰岛素作用的改变。这一切成功都 代谢紊乱能够改变特定底物 氧化和增加蛋白质和能量需求。整体 拟议研究的目的是确定HbSS对 全身和骨骼肌的营养代谢和需求。 已经设计了两个单独的协议来识别 蛋白质和能量需求增加的机制 HbSS期间。这些协议将1）定义营养物质的变化 HbSS期间的代谢改变能量代谢的基础和期间 模拟进食，2）确定是否增加 蛋白质和/或能量的可用性改善蛋白质稳态， HbSS患者3）确定蛋白质合成的需求， 红细胞和其他特定组织影响蛋白质和能量 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 重点关注与吸收后相关的事件，与饮食相关的事件， 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，营养输液， HbSS患者的正常血糖-高胰岛素钳夹。 当 结合起来，拟议的议定书将提高我们的理解， HbSS如何改变蛋白质和能量代谢， 这些变化的机制。HbSS对健康的贡献 护理成本是显着的，从这些研究中获得的知识 能让我们更好地理解各种代谢过程 与HbSS有关。这些知识将有助于设计 适当的营养方案，从而达到更好的 疾病结果。

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.