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dc.contributor.authorCoverdale, James P. C.
dc.contributor.authorKatundu, Kondwani G. H.
dc.contributor.authorSobczak, Amélie Isabelle Sylvie
dc.contributor.authorArya, Swati
dc.contributor.authorBlindauer, Claudia A.
dc.contributor.authorStewart, Alan J.
dc.date.accessioned2018-08-22T11:30:06Z
dc.date.available2018-08-22T11:30:06Z
dc.date.issued2018-08
dc.identifier.citationCoverdale , 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.2018.07.014en
dc.identifier.issn0952-3278
dc.identifier.otherPURE: 254989571
dc.identifier.otherPURE UUID: d840a029-870f-4a12-8591-31bbcb78b993
dc.identifier.otherScopus: 85051104665
dc.identifier.otherWOS: 000443663700020
dc.identifier.urihttp://hdl.handle.net/10023/15855
dc.descriptionThis 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).en
dc.description.abstractMyocardial 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.
dc.format.extent11
dc.language.isoeng
dc.relation.ispartofProstaglandins, Leukotrienes and Essential Fatty Acidsen
dc.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/).en
dc.subjectAlbumin cobalt binding assayen
dc.subjectMolecular diagnosticsen
dc.subjectFree fatty acidsen
dc.subjectHuman serum albuminen
dc.subjectMyocardial ischaemiaen
dc.subjectQD Chemistryen
dc.subjectR Medicineen
dc.subject.lccQDen
dc.subject.lccRen
dc.titleIschemia-modified albumin : crosstalk between fatty acid and cobalt bindingen
dc.typeJournal itemen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews.School of Medicineen
dc.contributor.institutionUniversity of St Andrews.Cellular Medicine Divisionen
dc.contributor.institutionUniversity of St Andrews.Biomedical Sciences Research Complexen
dc.contributor.institutionUniversity of St Andrews.Institute of Behavioural and Neural Sciencesen
dc.identifier.doihttps://doi.org/10.1016/j.plefa.2018.07.014
dc.description.statusPeer revieweden


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