A biophysical insight into structural and functional state of human serum albumin in uremia mimic milieu.

Abstract

In chronic kidney diseases (CKD), uremic toxins accumulate in the blood plasma of patients and interact with human serum albumin (HSA) and thus impaired its role as carrier protein. Present study shows in vitro effect of carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF), indoxyl sulfate (IS), indole-3 acetic acid (IAA), and hippuric acid (HA) with human serum albumin (HSA) at pathological concentrations. HSA bind with CMPF, IS and IAA at both of its binding sites with high affinity (order of 105 to 106 M-1) and low affinity (order of 103 to 105 M-1). Under pathological concentrations CMPF, IS, IAA and HA induce marked secondary structural alterations in HSA as observed by FTIR and CD measurements. Differential scanning calorimetry results show an increase in melting temperature (Tm) of HSA under mimicked pathological condition. Furthermore, hydrolase activity of HSA decreases in presence of CMPF, IS, IAA and HA as of their binding in vicinity of active site.