title: Thermodynamic analysis of human serum albumin interactions with glucose: insights into the diabetic range of glucose concentration.
abstract: The interaction of proteins with glucose results in their non-enzymatic glycation and influences their structural and functional properties. Human serum albumin (HSA) interacts with glucose forming glycated HSA. However, the glucose binding sites and the thermodynamic characteristics of the glycated HSA require further delineation. Here, the binding properties of HSA and glucose were studied utilizing fluorescent techniques. HSA was incubated with glucose in the 0-300mM range at 27 or 37 degrees C. The interaction of HSA with glucose showed two sets of binding sites. The first set consists of two sites with positive cooperativity and the second set consists of nine identical non-cooperative sites. The percentage of glycated HSA (gly%) and the moles of glucose bound to moles of HSA (r) were utilized to obtain binding constants and thermodynamic parameters based on the Wyman binding potential. The enthalpy of binding, obtained by van't Hoff relation, presented exothermicity up to 7mM glucose (126mg/dl, normal range) and endothermic propensity at higher glucose concentrations (>7mM, diabetic range). The start of endothermic propensity was consistent with the diabetic range of glucose concentration and indicates unfolding of HSA. The Gibbs free energy and entropy of binding further supports the unfolding of HSA. Therefore, glucose interacts with multiple sites on HSA affecting its biochemical and biophysical properties. This may interfere with HSA normal function contributing to diabetic complications.
authors: Institute of Biochemistry and Biophysics, University of Tehran, Iran.
authors: A
authors: A
authors: Mohamadi-Nejad
authors: A A
authors: AA
authors: Moosavi-Movahedi
authors: G H
authors: GH
authors: Hakimelahi
authors: N
authors: N
authors: Sheibani
mesh_terms: D001665:Binding Sites; D001786:Blood Glucose / Q000378:metabolism; D003920:Diabetes Mellitus / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006801:Humans; D008433:Mathematics; D011485:Protein Binding; D012709:Serum Albumin / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D013696:Temperature; D013816:Thermodynamics
chemical_list: D001786:Blood Glucose; D017127:Glycation End Products, Advanced; D012709:Serum Albumin; D005947:Glucose