Skip to content

Research at St Andrews

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

Research output: Contribution to journalReview articlepeer-review


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.


Original languageEnglish
Pages (from-to)147-157
Number of pages11
JournalProstaglandins, Leukotrienes and Essential Fatty Acids
Early online date20 Jul 2018
Publication statusPublished - Aug 2018

    Research areas

  • Albumin cobalt binding assay, Molecular diagnostics, Free fatty acids, Human serum albumin, Myocardial ischaemia

Discover related content
Find related publications, people, projects and more using interactive charts.

View graph of relations

Related by author

  1. Prognostic features of the tumour microenvironment in oesophageal adenocarcinoma

    McShane, R., Arya, S., Stewart, A. J., Caie, P. D. & Bates, M., 29 Jul 2021, (E-pub ahead of print) In: Biochimica et Biophysica Acta - Reviews on Cancer. 188598.

    Research output: Contribution to journalReview articlepeer-review

  2. Leptin and obesity: Role and clinical implication

    Obradovic, M., Sudar-Milovanovic, E., Soskic, S., Essack, M., Arya, S., Stewart, A. J., Gojobori, T. & Isenovic, E. R., 18 May 2021, In: Frontiers in Endocrinology. 12, 14 p., 585887.

    Research output: Contribution to journalReview articlepeer-review

  3. Albumin-mediated alteration of plasma zinc speciation by fatty acids modulates blood clotting in type-2 diabetes

    Sobczak, A. I. S., Katundu, K. G. H., Phoenix, F. A., Khazaipoul, S., Yu, R., Lampiao, F., Stefanowicz, F., Blindauer, C. A., Pitt, S. J., Smith, T. K., Ajjan, R. A. & Stewart, A. J., 21 Mar 2021, In: Chemical Science. 12, 11, p. 4079-4093 15 p.

    Research output: Contribution to journalArticlepeer-review

ID: 254989571