Allosteric modulation of zinc speciation by fatty acids

James P. Barnett, Claudia A. Blindauer, Omar Kassaar, Siavash Khazaipoul, Esther M. Martin, Peter J. Sadler, Alan J. Stewart

Research output: Contribution to journalArticlepeer-review

45 Citations (Scopus)
5 Downloads (Pure)

Abstract

Background: 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.
Scope of Review: 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 is considered.
Major Conclusions: 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.
General Significance: 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.
Original languageEnglish
Pages (from-to)5456-5464
Number of pages9
JournalBiochimica et Biophysica Acta - General Subjects
Volume1830
Issue number12
Early online date29 May 2013
DOIs
Publication statusPublished - Dec 2013

Keywords

  • Allostery
  • Circulation
  • Fatty acids
  • Protein-lipid interaction
  • Protein-metal interaction
  • Serum albumin
  • Zinc

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