Allosteric modulation of zinc speciation by fatty acids |
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Authors: | James P Barnett Claudia A Blindauer Omar Kassaar Siavash Khazaipoul Esther M Martin Peter J Sadler Alan J Stewart |
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Institution: | 1. Department of Chemistry, University of Warwick, Coventry, CV4 7AL, UK;2. School of Medicine, University of St Andrews, St Andrews, KY16 9TF, UK;3. Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong |
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Abstract: | BackgroundSerum albumin is the major protein component of blood plasma and is responsible for the circulatory transport of a range of small molecules that include fatty acids, hormones, metal ions and drugs. Studies examining the ligand-binding properties of albumin make up a large proportion of the literature. However, many of these studies do not address the fact that albumin carries multiple ligands (including metal ions) simultaneously in vivo. Thus the binding of a particular ligand may influence both the affinity and dynamics of albumin interactions with another.Scope of reviewHere we review the Zn2 + and fatty acid transport properties of albumin and highlight an important interplay that exists between them. Also the impact of this dynamic interaction upon the distribution of plasma Zn2 +, its effect upon cellular Zn2 + uptake and its importance in the diagnosis of myocardial ischemia are considered.Major conclusionsWe previously identified the major binding site for Zn2 + on albumin. Furthermore, we revealed that Zn2 +-binding at this site and fatty acid-binding at the FA2 site are interdependent. This suggests that the binding of fatty acids to albumin may serve as an allosteric switch to modulate Zn2 +-binding to albumin in blood plasma.General significanceFatty acid levels in the blood are dynamic and chronic elevation of plasma fatty acid levels is associated with some metabolic disorders such as cardiovascular disease and diabetes. Since the binding of Zn2 + to albumin is important for the control of circulatory/cellular Zn2 + dynamics, this relationship is likely to have important physiological and pathological implications. This article is part of a Special Issue entitled Serum Albumin. |
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Keywords: | ACB albumin-cobalt-binding ATCUN amino-terminal copper and nickel binding BSA bovine serum albumin EXAFS extended X-ray absorption spectroscopy FA1&ndash 7 fatty acid-binding sites 1&ndash 7 HRG histidine-rich glycoprotein HRR histidine-rich region HSA human serum albumin IMA ischemia-modified albumin ITC isothermal titration calorimetry MI myocardial ischemia mol eq molar equivalents TCA tricarboxylic acid |
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