Abstract
Human serum albumin (HSA) constitutes the primary transporter of fatty acids, bilirubin, and other plasma compounds. The binding, transport, and release of its cargos strongly depend on albumin conformation, which is affected by bound ligands induced by physiological and pathological conditions. HSA is both highly oxidized and heavily loaded with fatty acids and bilirubin in chronic liver disease. By employing small-angle X-ray scattering we show that HSA from the plasma of chronic liver disease patients undergoes a distinct opening compared to healthy donors. The extent of HSA opening correlates with clinically relevant variables, such as the model of end-stage liver disease score, bilirubin, and fatty acid levels. Although the mild oxidation of HSA in vitro does not alter overall structure, the alteration of patients’ HSA correlates with its redox state. This study connects clinical data with structural visualization of albumin dynamicity in solution and underlines the functional importance of albumin’s inherent flexibility.
Highlights
Human serum albumin (HSA) constitutes the primary transporter of fatty acids, bilirubin, and other plasma compounds
We show that the HSA dynamicity in solution correlates with the increased level of lipid, bilirubin, and redox state and informs the structural mechanism relevant to liver disease
Upon binding of dansylsarcosine (DS) Kd ranged from 13–28 μmol/L in patients’ HSA and from 12–18 μmol/L in HSA of healthy donors
Summary
Human serum albumin (HSA) constitutes the primary transporter of fatty acids, bilirubin, and other plasma compounds. The detoxification efficiency of HSA may vary in vivo due to the conformational changes upon interactions with surfaces, like cells[6,7], or upon binding of different ligands, foremost FA and bilirubin[8,9]. This is especially relevant in liver disease as both FA and bilirubin in plasma may be increased substantially in these pathologies. Within aging and end-stage liver diseases, the redox state of HSA is shifted to the oxidized fractions, with implications for its transport function[11,14,15,16]. HSA can be separated into three different fractions according to the redox state of its cysteine residue
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