Characterization of Spontaneous Sugar Modifications of Proteins
In: Student Reports, Summer 2022, The Jackson Laboratory
Brian Hoffmann, Ph.D.
Diabetes is one of the most prevalent diseases in the United States and causes many people to be susceptible to other health risks such as heart disease. Due to the hyperglycemic environment of blood in diabetic patients, many proteins can be modified through glycation (spontaneous glycosylation), which has the potential to inhibit protein function depending on site of modification. In this study, we looked to elucidate the conditions that induce protein glycation. To do this, we used a short peptide with known glycosylation consensus sequences. This peptide was then treated with different concentrations (0-250mM) of various sugars (glucose, fructose) and the modifications were observed over time (0-7 days) using intact and liquid chromatography tandem mass spectrometry analysis. In this study, we found that glycosylation is a time dependent reaction, less than a concentration dependent reaction, as it can occur at lower glycemic ranges. Each of the varying glucose concentrations plateaued at about 50% modified and reached this point at one week. Based on the data collected, concentration has some impact on fructose modification the higher concentrations (100mM and 250mM) reached almost 17% modified after 1 week while the lower concentrations (25mM and 50mM) only about 10% modified. We also found that glucose is much more reactive than fructose with glucose reaching 50% modification, while fructose only reached about 16% modification. These results suggest that under favorable conditions glucose and to a lesser extent fructose can induce significant glycation of proteins during hyperglycemia that could have adverse effects on protein function. Once these glycation reactions are better defined we will be able to pursue therapeutic intervention through altering the environment for these reactions.
Sabol, Lily, "Characterization of Spontaneous Sugar Modifications of Proteins" (2022). Summer and Academic Year Student Reports. 2713.