Biophysical Insight into Furosemide Binding to Human Serum Albumin: A Study To Unveil Its Impaired Albumin Binding in Uremia

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• 作者：Nida Zaidi ; Ejaz Ahmad ; Mohd Rehan ; Gulam Rabbani ; Mohammad R. Ajmal ; Yusra Zaidi ; Naidu Subbarao ; Rizwan H. Khan
• 刊名：The Journal of Physical Chemistry B
• 出版年：2013
• 出版时间：March 7, 2013
• 年：2013
• 卷：117
• 期：9
• 页码：2595-2604
• 全文大小：580K
• 年卷期：v.117,no.9(March 7, 2013)
• ISSN：1520-5207

文摘

Exogenous substances like drugs, when absorbed, enter into the circulatory system and bind reversibly and extensively to human serum albumin (HSA). But transport of various drugs like a diuretic, furosemide (FUR), via albumin in uremia is seriously compromised due to accumulation of uremic toxins. The reason behind it is explored by investigating the binding mechanism of FUR to HSA. Isothermal titration calorimetry results show that FUR binds with HSA at high (K_b 10⁴) and low affinity (K_b 10³) sites whereas spectroscopic results predict binding at a single site (K_b 10⁵). Thermodynamic analysis shows that the HSA-FUR complex formation occurs via hydrogen bonds and hydrophobic interactions and undergoes slight structural changes, as evident by FTIR and far-UV CD. Further, the lifetime of HSA decreases only marginally and thus the magnitude of energy transfer efficiency is small, as obtained by time-resolved measurements. A displacement experiment predicts that the FUR binds mainly to site I but a new site having lower affinity is also observed, which shares some residues with site II as supported by molecular docking results. Results revealed that in uremia, FUR indirectly competes for Arg410, Lys414, and Ser489 with site II bound uremic toxins and directly competes for site I with site I bound uremic toxins.