Nonenzymatic glucosylation of human serum albumin and its influence on binding capacity of sulfonylureas.
To estimate the functional change occurring in human serum albumin by nonenzymatic glucosylation, glucosylated human serum albumin was prepared by in vitro incubation with glucose. The rate of glucosylation proceeded as a first-order reaction. The binding of sulfonylureas to serum albumin was determined by equilibrium gel filtration. Through this method, it was possible to estimate the binding capacity of a low water solubility drug with a high affinity to protein. The amounts of the sulfonylureas bound to glucosylated HSA decreased by 44% with tolazamide and acetohexamide, 50% with glibenclamide, and 52% with tolbutamide, compared to human serum albumin (HSA). This suggests that a high concentration of glucosylated HSA in diabetic patients may possibly cause an increase in free drug concentration exceeding normal levels. This study shows that the decrease in the binding capacity of sulfonylureas with protein is due to the modification of albumin molecules by the covalent binding of glucose.
D002846:Chromatography, Affinity; D002850:Chromatography, Gel; D003920:Diabetes Mellitus / Q000378:metabolism; D017127:Glycation End Products, Advanced; D006801:Humans; D066298:In Vitro Techniques; D011485:Protein Binding; D012709:Serum Albumin / Q000378:metabolism*; D013453:Sulfonylurea Compounds / Q000378:metabolism*; D000093423:Glycated Serum Albumin
D017127:Glycation End Products, Advanced; D012709:Serum Albumin; D013453:Sulfonylurea Compounds; D000093423:Glycated Serum Albumin