New insights into non-enzymatic glycation of human serum albumin biopolymer: A study to unveil its impaired structure and function.
Albumin glycation and subsequent formation of advanced glycation end products (AGEs) correlate with diabetes and associated complications. Human Serum Albumin (HSA) was modified with d-glucose for a 40day period under sterile conditions at 37°C. Modified samples along with native HSA (unmodified) were analyzed for impairment in biochemical characteristics ((fructosamine, carbonyl, thiol, lysine, arginine, hydroxymethyl furfural [HMF] content), electrochemical (electrical conductance), simulated gastric fluid assay, simulated intestinal fluid assay, spectroscopic properties (UV, fluorescence), optical (surface contact angle) and fluid dynamics (viscosity and Stokes radius). Impairment in drug binding capacity of glycosylated-HSA was assessed with molecular docking experiment using metformin. UV-absorbance and fluorescence measurement were performed for drug bound glycated and native-HSA. Extensively modified HSA has been used to study its relevance in diabetes mellitus. Glucose modified-HSA resulted in AGEs formation. It suggests deleterious impairment in biochemical, electrochemical, spectroscopic, optical and fluidity properties of HSA at high concentrations of glucose. The results of the present study can be useful to understand the phenomenon of proteins damage in hyperglycemic conditions.
Rajiv Gandhi Centre for Diabetes & Endocrinology, J.N. Medical College, Aligarh Muslim University, Aligarh, UP, 202002, India.
Alok
A
Raghav
Rajiv Gandhi Centre for Diabetes & Endocrinology, J.N. Medical College, Aligarh Muslim University, Aligarh, UP, 202002, India. Electronic address: jamalahmad11@rediffmail.com.
Jamal
J
Ahmad
Department of Biochemistry, Faculty of Medicine, J.N. Medical College, Aligarh Muslim University, Aligarh, UP, 202002, India.
Khursheed
K
Alam
Interdsciplianry Biotechnology UnitAligarh Muslim University, Aligarh, UP, 202002, India.
Asad U
AU
Khan
D017127:Glycation End Products, Advanced / Q000378:metabolism; D006801:Humans; D008687:Metformin / Q000378:metabolism; D062105:Molecular Docking Simulation; D011487:Protein Conformation; D012709:Serum Albumin / Q000737:chemistry* / Q000378:metabolism*; D000093423:Glycated Serum Albumin
D017127:Glycation End Products, Advanced; D012709:Serum Albumin; D008687:Metformin; D000093423:Glycated Serum Albumin
Advanced glycation end products; Albumin; Diabetes mellitus; Glucose; Glycation; Proteomics