The structure and function of human serum albumin in the normal and diseased states
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Human serum albumin (HSA) is the major protein in human serum and an important carrier of free fatty acids and small-molecule drugs. Various post-translationally modified forms of HSA, including glycated and oxidized HSA, are implicated in a variety of diseases, including cardiovascular disease and diabetes. In this study, the structure and stability of HSA was investigated through circular dichroism and fluorescence spectroscopy. The features of fatty acid-free HSA, fatty acid-bound HSA, and post-translationally modified protein forms, including cystenylated, glycated, oxidized, and glycoxidized HSA, were compared. The pro- or anti-oxidant effect of these various forms was studied through examining the oxidation of LDL by Cu ions in the presence of each of these forms of HSA. The results showed that fatty acid binding did not significantly alter the structural, stability or anti-oxidant properties of HSA. However, all post-translational modifications of HSA reversed its effect on LDL oxidation: unmodified HSA was clearly anti-oxidant, while modified HSA acted as a pro-oxidant by decreasing the lag phase of LDL oxidation. To our knowledge, this effect has not been reported previously. The biochemical and structural basis underlying this general effect and its relevance to various oxidation processes in vivo remains to be determined in the future. As the modified forms of HSA studied here are implicated in a variety of disease states, these studies could suggest significant changes to the functional properties of human serum albumin resulting from these post-translational modifications.
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