THE MAILLARD REACTION BETWEEN RIBOSE 5-PHOSPHATE AND CELLULAR AMINES

5-磷酸核糖与细胞胺之间的美拉德反应

• 批准号: 7725267
• 负责人: ROGER K SANDWICK
• 金额: $ 8.49万
• 依托单位: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7725267
• 关键词: Address; Advanced Glycosylation End Products; Amines; Area; Attention; Biochemistry; Cells; Computer Retrieval of Information on Scientific Projects Database; Diabetes Mellitus; Disease; Funding; Glucose; Goals; Grant; Institution; Kinetics; Laboratories; Maillard Reaction; Methods; Nature; Pentosephosphate Pathway; Proteins; Rate; Reaction; Reporting; Research; Research Personnel; Resources; Series; Source; System; United States National Institutes of Health; Work; crosslink; gel electrophoresis; glycation; improved; in vivo; link protein; liquid chromatography mass spectrometry; ribose-5-phosphate; sugar

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The spontaneous Maillard reaction between sugars and amines has been implicated in the formation of a variety of physiologically harmful compounds termed advanced glycation end-products (AGEs). While most attention in this research area has been focused on the common sugar glucose, recent reports show the pentose phosphate pathway metabolite ribose 5-phosphate (R5P) to undergo Maillard reactions with amines and proteins at significantly higher rates. Little is currently known about the nature of the R5P-derived glycation products or whether the reaction could potentially serve as an important contributor to AGEs formation in the body. This project investigates the reaction of R5P with amines and proteins with a long-term goal towards evaluating its significance in the cell. Work over the past year in our laboratory has thoroughly characterized the kinetics of the R5P-simple amine reaction systems, yielding results that are suggestive of a traditional, albeit faster, set of early Maillard reaction steps. The current project will expand this understanding, focusing primarily on the identification of intermediates and final products in the R5P Maillard reaction series and on the glycation mechanism (and potential cross-linking) of proteins. Along with traditional methods, liquid chromatography-mass spectrometry methods will be employed to determine reaction intermediates and gel electrophoresis studies will be used for establishing R5P-protein reactions. Overall, the project evaluates whether the metabolite ribose 5-phosphate is reacting with cellular amines to generate potentially toxic products in vivo. It is reasonable that R5P-derived glycation products could cause harmful effects in a manner similar to the glucose-derived advanced glycation end-products (AGEs) formed in diabetes and other diseases. While the project specifically addressed the R5P-promoted reaction, the ultimate goal is an improved understanding of the general biochemistry of AGEs and their cellular effects.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 糖和胺之间的自发美拉德反应与多种被称为晚期糖基化终末产物(AGEs)的生理有害化合物的形成有关。虽然这一研究领域的大部分注意力都集中在常见的糖-葡萄糖上，但最近的报道显示，磷酸戊糖途径的代谢产物5-磷酸核糖(R5P)与胺和蛋白质发生美拉德反应的速度明显更快。目前，人们对R5P衍生的糖基化产物的性质或该反应是否可能成为体内AGEs形成的重要贡献者知之甚少。该项目研究R5P与胺和蛋白质的反应，长期目标是评估其在细胞中的意义。我们实验室在过去一年的工作已经彻底表征了R5P-单胺反应体系的动力学，产生了一套传统的、尽管更快的早期美拉德反应步骤。目前的项目将扩大这一理解，主要侧重于R5P美拉德反应系列的中间体和最终产物的鉴定，以及蛋白质的糖基化机制(和潜在的交联)。除了传统的方法外，还将使用液相色谱-质谱法来确定反应中间产物，并将使用凝胶电泳研究来建立R5P-蛋白质反应。 总体而言，该项目评估代谢物5-磷酸核糖是否在体内与细胞胺反应产生潜在的有毒产物。R5P衍生的糖基化产物可能会造成类似于糖尿病和其他疾病中形成的葡萄糖衍生的晚期糖基化终末产物(AGEs)的有害影响，这是合理的。虽然该项目专门针对R5P促进的反应，但最终目标是改善对AGEs及其细胞效应的一般生物化学的理解。