Document Detail

Allosteric Inhibition of Cobalt Binding to Albumin by Fatty Acids: Implications for the Detection of Myocardial Ischemia.
MedLine Citation:
PMID:  22519414     Owner:  NLM     Status:  Publisher    
The biomarker "Ischemia-Modified Albumin" (IMA), measured by the albumin-cobalt-binding assay (ACB assay), is the only FDA-approved biomarker for early diagnosis of myocardial ischemia. Based on the hypothesis that high levels of free fatty acids are directly responsible for reduction in cobalt binding by albumin, chemically defined model systems consisting of BSA, Co<sup>2+</sup>, and myristate were studied by Isothermal Titration Calorimetry, <sup>111</sup>Cd NMR spectroscopy, and ACB assays. Significantly reduced Co<sup>2+</sup> binding to albumin, as demonstrated by an increase in absorption of the Co-dithiothreitol adduct, elicited by adding ca. 3 molar equivalents of myristate was comparable to that observed in clinical ACB assays. Levels of free fatty acids are elevated during myocardial ischemia, but also in other conditions that have been correlated with high IMA values. Hence, IMA may correspond to albumin with increased levels of bound fatty acids, and all clinical observations can be rationalised by this molecular mechanism.
Jin Lu; Alan J Stewart; Peter John Sadler; Teresa J T Pinheiro; Claudia Andrea Blindauer
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-4-23
Journal Detail:
Title:  Journal of medicinal chemistry     Volume:  -     ISSN:  1520-4804     ISO Abbreviation:  -     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-4-23     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9716531     Medline TA:  J Med Chem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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