Carbohydrate and Protein Metabolic Pathways

碳水化合物和蛋白质代谢途径

• 批准号: 6623781
• 负责人: BERNARD R LANDAU
• 金额: $ 37.46万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1978
• 资助国家: 美国
• 起止时间: 1978-05-01 至 2005-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6623781
• 关键词: body water; carbohydrate metabolism; clinical research; enzyme activity; fasting; gluconeogenesis; glucose metabolism; glycerol; glycogenesis; hemodialysis; human subject; hydrolysis; hyperglycemia; kidney metabolism; lipid metabolism; lipolysis; liver metabolism; method development; noninsulin dependent diabetes mellitus; protein biosynthesis; protein metabolism; proteolysis; renal failure; transaldolase /transketolase

DESCRIPTION (Provided by applicant): Carbohydrate, protein and lipid abnormalities characterize diabetes mellitus. Long-term objectives are to develop and apply novel methods significantly advancing understanding of those metabolic processes and their regulation in physiological and pathological states in human, and particularly in diabetes. Advantage is taken of 2H2O use to quantitate the pathways followed. Methods have been introduced for carbohydrate and lipid. The major new goal is to develop and apply a method for quantitating protein metabolism. The method for quantitating carbohydrate metabolism will also be further extended. Focus then is on 1) the quantitation of protein synthesis and proteolysis; 2) the contribution to glucose production of gluconeogenesis whose increase in diabetes has been related to the degree of hyperglycemia and 3) the extent of simultaneous hepatic glycogen synthesis and breakdown, called glycogen cycling, which could help explain decreased liver glycogen content found in type 2 diabetes and exacerbate hyperglycemia on glucose ingestion. There are 4 specific aims: 1) To develop and apply a method for quantitating the extent transaldolase reactions contribute to estimates of gluconeogenesis; 2) To evaluate the validity of a method using glucose isotopomers, introduced as a simple method to measure the contribution of gluconeogenesis, in comparison with 2H2O use; 3) To develop a method for quantitating glycogen cycling in the fed state by measuring, along with the rate of hepatic glycogen deposition on glucose intake, how much of the glycogen is formed directly from the glucose, how much from three carbon compounds, and how much from glycogen that is reconverted to glycogen, i.e. glycogen cycling; 4) To develop a method to estimate protein synthesis from labeling of protein by 2H2O, and proteolysis from loss of that label. Initial application of this method will be to renal failure patients undergoing hemodialysis, in whom ingested 2H2O can be removed by dialysis to readily follow loss of incorporated label without continued synthesis of labeled protein. Application first to the renal failure state is done with recognition that nephropathy is a major complication in the diabetic and the potential benefit of a simple method for evaluating the effects of the therapeutic approaches on protein dynamics in that condition.

性状（由申请人提供）：碳水化合物、蛋白质和脂质 异常是糖尿病的特征。长期目标是 开发和应用新的方法，大大提高对这些问题的理解， 代谢过程及其调节在生理和病理中的作用 尤其是在糖尿病中。利用2 H2O的使用 来量化所遵循的路径。方法已被引入， 碳水化合物和脂质。主要的新目标是开发和应用一种方法， 定量蛋白质代谢。碳水化合物的定量方法 新陈代谢也将进一步延长。重点是1）定量 蛋白质合成和蛋白质水解; 2）对葡萄糖产生的贡献 糖尿病的增加与糖尿病的程度有关。 高血糖和3）同时肝糖原合成的程度， 分解，称为糖原循环，这可以帮助解释肝脏减少 2型糖尿病患者的血糖水平明显升高。 葡萄糖摄入有4个具体目标：1）开发和应用一种方法 用于定量转醛醇酶反应有助于估计 2）评价葡萄糖法的有效性 同位素，介绍了作为一种简单的方法来衡量的贡献， 与2 H2O使用相比， 通过测量定量进食状态下的糖原循环，沿着 葡萄糖摄入量对肝糖原沉积的影响， 直接由葡萄糖形成，有多少是由三碳化合物形成的， 有多少糖原被再转化为糖原，即糖原循环; 4)建立一种通过标记蛋白质来预测蛋白质合成的方法 通过2 H2O，和蛋白质水解从该标签的损失。首次应用此 方法将是肾衰竭患者接受血液透析，其中 摄入的2 H2O可以通过透析去除，以容易地跟踪结合的2 H2O的损失。 标记而不继续合成标记蛋白质。申请先到 肾功能衰竭是一种慢性肾功能衰竭。 糖尿病并发症和一种简单方法的潜在益处 评估治疗方法对蛋白质动力学的影响， 这个条件。