title: Allosteric modulation of zinc speciation by fatty acids.
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.
  
  
  METHODS
  Here we review the Zn(2+) 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 Zn(2+), its effect upon cellular Zn(2+) uptake and its importance in the diagnosis of myocardial ischemia are considered.
  
  
  CONCLUSIONS
  We previously identified the major binding site for Zn(2+) on albumin. Furthermore, we revealed that Zn(2+)-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 Zn(2+)-binding to albumin in blood plasma.
  
  
  CONCLUSIONS
  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 Zn(2+) to albumin is important for the control of circulatory/cellular Zn(2+) dynamics, this relationship is likely to have important physiological and pathological implications. This article is part of a Special Issue entitled Serum Albumin.
authors.affiliation: Department of Chemistry, University of Warwick, Coventry, CV4 7AL, UK.
authors.forename: James P
authors.initials: JP
authors.lastname: Barnett
authors.forename: Claudia A
authors.initials: CA
authors.lastname: Blindauer
authors.forename: Omar
authors.initials: O
authors.lastname: Kassaar
authors.forename: Siavash
authors.initials: S
authors.lastname: Khazaipoul
authors.forename: Esther M
authors.initials: EM
authors.lastname: Martin
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Sadler
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Stewart
mesh_terms: D000494:Allosteric Regulation; D005227:Fatty Acids / Q000097:blood* / Q000737:chemistry; D006801:Humans; D017136:Ion Transport; D008958:Models, Molecular; D011485:Protein Binding; D012709:Serum Albumin / Q000737:chemistry / Q000378:metabolism*; D015032:Zinc / Q000097:blood* / Q000737:chemistry
chemical_list: D005227:Fatty Acids; D012709:Serum Albumin; D015032:Zinc
keywords: ACB; ATCUN; Allostery; BSA; Circulation; EXAFS; FA1–7; HRG; HRR; HSA; IMA; ITC; MI; Protein–lipid interaction; Protein–metal interaction; Serum albumin; TCA; Zinc; albumin-cobalt-binding; amino-terminal copper and nickel binding; bovine serum albumin; extended X-ray absorption spectroscopy; fatty acid-binding sites 1–7; histidine-rich glycoprotein; histidine-rich region; human serum albumin; ischemia-modified albumin; isothermal titration calorimetry; mol. eq.; molar equivalents; myocardial ischemia; tricarboxylic acid