This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor 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.
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