Allosteric Inhibition of Cobalt Binding to Albumin by Fatty Acids: Implications for the Detection of Myocardial Ischemia
Allosteric Inhibition of Cobalt Binding to Albumin by Fatty Acids: Implications for the Detection of Myocardial Ischemia
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DOI：
10.1021/jm3003137
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发表时间：
2012-05-10
影响因子：
7.3
通讯作者：
Blindauer, Claudia A.
中科院分区：
文献类型：
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作者：
Lu, Jin;Stewart, Alan J.;Blindauer, Claudia A.
通过白蛋白-钴结合试验（ACB试验）测量的生物标志物“缺血修饰的白蛋白”（IMA）是FDA批准的用于早期诊断心肌缺血的唯一生物标志物。的假设的基础上，高水平的游离脂肪酸是直接负责减少钴结合白蛋白，化学定义的模型系统组成的牛血清白蛋白，钴2+，肉豆蔻酸酯进行了研究，等温滴定量热法，Cd-111 NMR光谱，和ACB测定。显着减少的钴2+结合到白蛋白，所示的增加的吸收的Co-二硫苏糖醇加合物，引起添加钙。3摩尔当量的肉豆蔻酸酯，与临床ACB测定中观察到的结果相当。游离脂肪酸水平在心肌缺血期间升高，但在与高IMA值相关的其他条件下也升高。因此，IMA可能对应于结合脂肪酸水平升高的白蛋白，所有临床观察结果都可以通过这种分子机制合理化。
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. On the basis of 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 bovine serum albumin, Co2+, and myristate were studied by isothermal titration calorimetry, Cd-111 NMR spectroscopy, and ACB assays. Significantly reduced Co2+ binding to albumin, as demonstrated by an increase in the absorption of the Co-dithiothreitol adduct, elicited by adding ca. 3 mol equiv 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 rationalized by this molecular mechanism.