Allosteric modulation of zinc speciation by fatty acids

• Published in: Biochimica et biophysica acta Vol. 1830; no. 12; pp. 5456 - 5464
• Main Authors: Barnett, James P., Blindauer, Claudia A., Kassaar, Omar, Khazaipoul, Siavash, Martin, Esther M., Sadler, Peter J., Stewart, Alan J.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.12.2013
• Subjects: Allosteric Regulation; Allostery; binding sites; blood plasma; Circulation; diabetes; drugs; fatty acids; Fatty Acids - blood; Fatty Acids - chemistry; hormones; Humans; Ion Transport; ligands; metal ions; Models, Molecular; myocardial ischemia; Protein Binding; Protein–lipid interaction; Protein–metal interaction; Serum albumin; Serum Albumin - chemistry; Serum Albumin - metabolism; Zinc; Zinc - blood; Zinc - chemistry; ACB; FA1–7; HRR; Allostery; Serum albumin; EXAFS; Zinc; Protein–metal interaction; mol. eq; BSA; ATCUN; TCA; HSA; ITC; HRG; IMA; MI; Protein–lipid interaction; Circulation; histidine-rich glycoprotein; ischemia-modified albumin; histidine-rich region; fatty acid-binding sites 1–7; isothermal titration calorimetry; amino-terminal copper and nickel binding; tricarboxylic acid; molar equivalents; albumin-cobalt-binding; extended X-ray absorption spectroscopy; myocardial ischemia; human serum albumin; bovine serum albumin
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/j.bbagen.2013.05.028

Serum 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. Here 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. We 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. Fatty 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. •Serum albumin is a transport molecule that simultaneously carries multiple ligands in blood plasma.•The Zn2+-binding and fatty acid transport properties of albumin are interdependent.•Binding of fatty acids to albumin may allosterically modulate Zn2+ dynamics in blood plasma.•Elevated plasma fatty acid levels are associated with some metabolic disorders.•Interplay between fatty acid and Zn2+ transport may have physiological and clinical consequences.