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Ischemia-modified albumin : crosstalk between fatty acid and cobalt binding

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Coverdale_2018_PLEFA_Albumin_CC.pdf (1.122Mb)
Date
08/2018
Author
Coverdale, James P. C.
Katundu, Kondwani G. H.
Sobczak, Amélie Isabelle Sylvie
Arya, Swati
Blindauer, Claudia A.
Stewart, Alan J.
Funder
British Heart Foundation
British Heart Foundation
BBSRC
The Leverhulme Trust
Grant ID
FS/15/42/31556
PG/15/9/31270
BB/J006467/1
RPG-2017-214
Keywords
Albumin cobalt binding assay
Molecular diagnostics
Free fatty acids
Human serum albumin
Myocardial ischaemia
QD Chemistry
R Medicine
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Abstract
Myocardial ischemia is difficult to diagnose effectively with still few well-defined biochemical markers for identification in advance, or in the absence of myocardial necrosis. “Ischemia-modified albumin” (IMA), a form of albumin displaying reduced cobalt-binding affinity, is significantly elevated in ischemic patients, and the albumin cobalt-binding (ACB) assay can measure its level indirectly. Elucidating the molecular mechanism underlying the identity of IMA and the ACB assay hinges on understanding metal-binding properties of albumin. Albumin binds most metal ions and harbours four primary metal binding sites: site A, site B, the N-terminal site (NTS), and the free thiol at Cys34. Previous efforts to clarify the identity of IMA and the causes for its reduced cobalt-binding capacity were focused on the NTS site, but the degree of N-terminal modification could not be correlated to the presence of ischemia. More recent work suggested that Co2+ ions as used in the ACB assay bind preferentially to site B, then to site A, and finally to the NTS. This insight paved the way for a new consistent molecular basis of the ACB assay: albumin is also the main plasma carrier for free fatty acids (FFAs), and binding of a fatty acid to the high-affinity site FA2 results in conformational changes in albumin which prevent metal binding at site A and partially at site B. Thus, this review advances the hypothesis that high IMA levels in myocardial ischemia and many other conditions originate from high plasma FFA levels hampering the binding of Co2+ to sites A and/or B. This is supported by biophysical studies and the co-association of a range of pathological conditions with positive ACB assays and high plasma FFA levels.
Citation
Coverdale , J P C , Katundu , K G H , Sobczak , A I S , Arya , S , Blindauer , C A & Stewart , A J 2018 , ' Ischemia-modified albumin : crosstalk between fatty acid and cobalt binding ' , Prostaglandins, Leukotrienes and Essential Fatty Acids , vol. 135 , pp. 147-157 . https://doi.org/10.1016/j.plefa.2018.07.014
Publication
Prostaglandins, Leukotrienes and Essential Fatty Acids
Status
Peer reviewed
DOI
https://doi.org/10.1016/j.plefa.2018.07.014
ISSN
0952-3278
Type
Journal item
Rights
© 2018 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/BY/4.0/).
Description
This work was supported by the Leverhulme Trust (grant ref. RPG-2017-214), BBSRC (grant ref. BB/J006467/1) and the British Heart Foundation (grant refs. PG/15/9/31270 and FS/15/42/31556).
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  • University of St Andrews Research
URI
http://hdl.handle.net/10023/15855

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