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Ischemia-modified albumin : crosstalk between fatty acid and cobalt binding
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Coverdale, James P. C., Katundu, Kondwani G. H., Sobczak, Amélie I. S., Arya, Swati, Blindauer, Claudia A. and Stewart, Alan J. (2018) Ischemia-modified albumin : crosstalk between fatty acid and cobalt binding. Prostaglandins, Leukotrienes and Essential Fatty Acids, 135 . pp. 147-157. doi:10.1016/j.plefa.2018.07.014 ISSN 0952-3278.
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WRAP-ischemia-modified-albumin-crosstalk-fatty-acid-cobalt-Coverdale-2018.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution 4.0. Download (1314Kb) | Preview |
Official URL: http://dx.doi.org/10.1016/j.plefa.2018.07.014
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.
| Item Type: | Journal Article | |||||||||||||||
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| Subjects: | R Medicine > RC Internal medicine | |||||||||||||||
| Divisions: | Faculty of Science, Engineering and Medicine > Science > Chemistry | |||||||||||||||
| SWORD Depositor: | Library Publications Router | |||||||||||||||
| Library of Congress Subject Headings (LCSH): | Silent myocardial ischemia , Coronary heart disease | |||||||||||||||
| Journal or Publication Title: | Prostaglandins, Leukotrienes and Essential Fatty Acids | |||||||||||||||
| Publisher: | Elsevier BV | |||||||||||||||
| ISSN: | 0952-3278 | |||||||||||||||
| Official Date: | August 2018 | |||||||||||||||
| Dates: |
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| Volume: | 135 | |||||||||||||||
| Page Range: | pp. 147-157 | |||||||||||||||
| DOI: | 10.1016/j.plefa.2018.07.014 | |||||||||||||||
| Status: | Peer Reviewed | |||||||||||||||
| Publication Status: | Published | |||||||||||||||
| Access rights to Published version: | Open Access (Creative Commons) | |||||||||||||||
| Date of first compliant deposit: | 19 September 2018 | |||||||||||||||
| Date of first compliant Open Access: | 20 September 2018 | |||||||||||||||
| RIOXX Funder/Project Grant: |
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