Ischemia-modified albumin: Crosstalk between fatty acid and cobalt binding.
Ischemia-modified albumin: Crosstalk between fatty acid and cobalt binding.
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DOI：
10.1016/j.plefa.2018.07.014
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发表时间：
2018-08
期刊：
影响因子：
--
通讯作者：
Stewart AJ
中科院分区：
文献类型：
--
作者：
Coverdale JPC;Katundu KGH;Sobczak AIS;Arya S;Blindauer CA;Stewart AJ
白蛋白-钴结合试验的分子机制。游离脂肪酸结合干扰Co（II）与白蛋白的结合。缺血修饰白蛋白对应于FFA结合增加的白蛋白。FFA水平升高足以解释ACB读数升高。临床数据与FFA作为高ACB/高IMA水平的触发因素一致。心肌缺血很难有效诊断，因为在没有心肌坏死的情况下，仍然很少有明确的生化标志物用于预先识别。“缺血修饰白蛋白”（IMA），一种表现出降低的钴结合亲和力的白蛋白形式，在缺血患者中显著升高，并且白蛋白钴结合（ACB）测定可以间接测量其水平。阐明IMA和ACB测定的分子机制取决于对白蛋白金属结合特性的理解。白蛋白结合大多数金属离子，并具有四个主要金属结合位点：位点A、位点B、N末端位点（NTS）和Cys 34处的游离巯基。以前的努力，以澄清IMA的身份和其钴结合能力降低的原因集中在NTS网站，但N-末端修饰的程度不能与缺血的存在。最近的研究表明，AC B测定中使用的Co 2+离子优先结合位点B，然后结合位点A，最后结合NTS。这一见解为AC B测定的新的一致分子基础铺平了道路：白蛋白也是游离脂肪酸（FFA）的主要血浆载体，脂肪酸与高亲和力位点FA 2的结合导致白蛋白的构象变化，从而阻止金属在位点A和部分位点B的结合。因此，这篇综述提出了一个假设，即心肌缺血和许多其他疾病中的高IMA水平源于高血浆FFA水平阻碍了Co2+与A和/或B位点的结合。这得到了生物物理学研究以及一系列病理状况与阳性ACB测定和高血浆FFA水平的共同关联的支持。
A molecular mechanism underlying the albumin-cobalt binding assay. Free fatty acid binding interferes with Co(II) binding to albumin. Ischemia-modified albumin corresponds to albumin with increased FFA bound. Increased FFA levels are sufficient to explain high ACB readings. Clinical data are consistent with FFA as the trigger for high ACB/high IMA levels. 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.
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影响因子：
4.2
作者：
CHILVERS, DC;DAWSON, JB;HODGKINSON, A
通讯作者：
HODGKINSON, A
影响因子：
5.8
作者：
Caraccio, N;Natali, A;Ferrannini, E
通讯作者：
Ferrannini, E
影响因子：
4.8
作者：
Bhardwaj, Anju;Truong, Quynh A.;Januzzi, James L., Jr.
通讯作者：
Januzzi, James L., Jr.
DOI：
10.1046/j.1432-1327.2001.01846.x
发表时间：
2001-01-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
Bar-Or, D;Curtis, G;Lau, E
通讯作者：
Lau, E
影响因子：
3.9
作者：
Bal, W;Christodoulou, J;Tucker, A
通讯作者：
Tucker, A