Metabolic analysis in human sulfur amino acid deficiency

人体硫氨基酸缺乏症的代谢分析

• 批准号: 6856472
• 负责人: Dean Paul Jones
• 金额: $ 15.3万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-03-01 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6856472
• 关键词: aminoacid metabolism; clinical research; glutathione; high throughput technology; human subject; nuclear magnetic resonance spectroscopy; nutrient intake activity; nutrient requirement; nutrition related tag; oxidation reduction reaction; oxidative stress; protein deficiency; sulfur aminoacid

DESCRIPTION (provided by applicant): Varied food intake, disease and genetic differences result in complex diet-health interactions. In principle, information-rich metabolic analyses combined with bioinformatic tools provide an approach to explore these interactions. This project is a feasibility study of the use of high-resolution 1H-NMR to study metabolic perturbations induced by deficiency in sulfur amino acids (SAA). In cell culture, sulfur amino acid (SAA) deficiency results in substantial oxidation of glutathione (GSH) redox state. Because GSH redox affects central homeostatic and cell defense mechanisms, redox changes in vivo due to SAA deficiency could induce complex physiologic effects that are not easily predictable by more traditional metabolic analyses. We will 1) test the hypothesis that deficient dietary intake of SAA in humans results in oxidation of GSH/GSSG redox and 2) determine whether 1H-NMR of blood and urine detects metabolic changes due to SAA deficiency. Studies will be performed on 12 healthy individuals (6 males, 6 females) in the Emory General Clinical Research Center (GCRC) using a crossover design (replete, deficient, replete). Kinetic and balance studies will establish the time course and magnitude of changes in SAA and metabolites in blood and urine in response to SAA intake. Plasma GSH/GSSG and cysteine/cystine redox will be measured to determine whether variation in intake of SAA affects steady-state thiol-disulfide redox state. 1H-NMR spectra of blood and urine samples will be used to determine whether metabolic changes unrelated to the direct SAA metabolites can be detected in association with variation in SAA intake. The results will show whether variation in SAA intake is likely to affect health risks associated with thiol-disulfide redox and oxidative stress. Furthermore, because NMR analysis of biofluids can be performed with a high throughput (e.g., 300 samples/day with a flow cell), results will show whether this approach could be useful for nutritional assessment of complex metabolic effects of SAA intake.

描述（由申请人提供）： 不同的食物摄入量，疾病和遗传差异导致复杂的饮食与健康的相互作用。原则上，信息丰富的代谢分析与生物信息学工具相结合，提供了一种探索这些相互作用的方法。本项目是利用高分辨率1H-NMR研究含硫氨基酸（SAA）缺乏引起的代谢紊乱的可行性研究。在细胞培养中，含硫氨基酸（SAA）缺乏导致谷胱甘肽（GSH）氧化还原态的大量氧化。由于GSH氧化还原影响中枢稳态和细胞防御机制，SAA缺乏导致的体内氧化还原变化可能会诱导复杂的生理效应，这些效应不容易通过更传统的代谢分析预测。我们将1）测试以下假设：人类SAA的饮食摄入不足导致GSH/GSSG氧化还原的氧化，以及2）确定血液和尿液的1H-NMR是否检测到由于SAA缺乏引起的代谢变化。将在Emory General Clinical Research Center（GCRC）采用交叉设计（完全、缺乏、完全）对12名健康个体（6名男性，6名女性）进行研究。动力学和平衡研究将确定SAA以及血液和尿液中代谢物响应SAA摄入的变化的时程和幅度。将测量血浆GSH/GSSG和半胱氨酸/胱氨酸氧化还原，以确定SAA摄入量的变化是否影响稳态硫醇-二硫化物氧化还原状态。血液和尿液样本的1H-NMR光谱将用于确定是否可以检测到与SAA直接代谢物无关的代谢变化与SAA摄入量的变化相关。结果将显示SAA摄入量的变化是否可能影响与硫醇-二硫化物氧化还原和氧化应激相关的健康风险。此外，由于生物流体的NMR分析可以以高通量（例如，300个样品/天，使用流动池），结果将显示这种方法是否可用于SAA摄入的复杂代谢效应的营养评估。