During diabetes, human serum albumin (HSA) is modified by reactive dicarbonyl compounds such as methylglyoxal (MGO) and glyoxal (GO). These compounds react with the lysine and arginine residues on HSA to form advanced glycation end-products (AGEs) which have been implicated in diabetes and its complications. This study characterized the metabolic effects of diabetes on the structure and function of HSA. High-performance affinity chromatography (HPAC) was used to investigate the changes in the binding that occur with MGO and GO modified HSA. Zonal elution studies were carried out with repaglinide (a drug used in treating diabetes) on columns that contained HSA or modified HSA prepared <i>in vitro</i>. R-warfarin and L-tryptophan were used as site-selective probes for Sudlow sites I and II of HSA. The structural alterations in HSA caused by the different levels of MGO and GO were evaluated. Mass spectrometry experiment based on high-resolution matrix-assisted laser desorption/ionization Fourier-transform ion-cyclotron resonance mass spectrometer (MALDI/FTICR MS) was used to obtain qualitative structural information on the glycation-related modifications that occurred in the modified HSA samples. The differences in the function and structure of HSA and the different levels of MGO and GO modified HSA were compared. This information is needed to better understand the metabolic effects of diabetes on drug binding with HSA being a major transport protein for drugs and the effects of glycation on this protein which could be used in the future to develop improved treatment protocols for diabetes patients.

Analysis of the metabolic effects of diabetes on the function and structure of glyoxal and methylglyoxal modified human serum albumin

ACS Spring Meeting 2021

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