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

Publication date: Available online 20 July 2018Source: Prostaglandins, Leukotrienes and Essential Fatty AcidsAuthor(s): James P.C. Coverdale, Kondwani Katundu, Amélie I.S. Sobczak, Swati Arya, Claudia A. Blindauer, Alan J. StewartAbstractMyocardial 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-affin...

Source: Prostaglandins, Leukotrienes and Essential Fatty Acids (PLEFA) - July 21, 2018 Category: Lipidology Source Type: research