Interactions of very long-chain saturated fatty acids with serum albumin
Interactions of very long-chain saturated fatty acids with serum albumin
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DOI：
10.1194/jlr.m200041-jlr200
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发表时间：
2002-07-01
影响因子：
6.5
通讯作者：
Hamilton, JA
中科院分区：
文献类型：
--
作者：
Choi, JK;Ho, J;Hamilton, JA
血清白蛋白的显著结合特性已被广泛研究，但对一类重要的脂肪酸--超长链饱和脂肪酸(VLCFA；>；118 Carons)却知之甚少。虽然VLCFA在正常人体内代谢效率很高，但它们是几种过氧酶体疾病的标志物和可能的致病因素。用~(13)C-核磁共振波谱研究了富含[C-13]羧基的阿魏酸(C20：0)、山毛酸(C22：0)、甘油酸(C24：0)和十六烷酸(C26：0)与牛血清白蛋白(BSA)的结合作用。对于每个VLCFA，核磁共振谱显示了先前确定的长链脂肪酸(12-18个碳)的化学位移处的多个信号，这表明脂肪酸羧基阴离子与碱性氨基酸残基的作用类似(如果不是相同的话)使结合稳定。最大结合(VLCFA/BSA摩尔)和观察到的结合位点数随着链长的增加而减少，C20：0为4-5，C22：0为3-4，C24：0为2；我们验证了我们先前的结论，即BSA与C26：0只有一个结合位点(Ho，J.K.，H.Moser，Y.Kishimoto和J.A.Hamilton)。1995年。J·克莱恩。投资。96：1455-1463)。化学位移分析表明，VLCFA的亲和力最高的部位是长链脂肪酸的低亲和力部位。在与C-13标记的C22：0(3摩尔/摩尔牛血清白蛋白)和未标记油酸的竞争实验中，当油酸/牛血清白蛋白的摩尔浓度高达4摩尔时，C22：0与牛血清白蛋白结合，但I摩尔发生了移位。我们的研究表明，白蛋白与20-26个碳的低水平VLCFA有足够的结合能力，但可能不能与较长链的VLCFA结合。
The remarkable binding properties of serum albumin have been investigated extensively, but little is known about an important class of fatty acids, the very long-chain saturated fatty acids (VLCFA; > 118 carbons). Although VLCFA are metabolized efficiently in normal individuals, they are markers for and possibly causative agents of several peroxisomal disorders. We studied the binding of [C-13]carboxyl-enriched arachiclic (C20:0), behenic (C22:0), lignoceric (C24:0), and hexacosanoic (C26:0) acids to bovine serum albumin (BSA) by C-13-NMR spectroscopy. For each VLCFA, the NMR spectra showed multiple signals at chemical shifts previously identified for long-chain fatty acids (12-18 carbons), suggesting stabilization of binding by similar, if not identical, interactions of the fatty acid carboxyl anion with basic amino acid residues. The maximal binding (mol of VLCFA/mol of BSA) and the number of observed binding sites decreased with increasing chain length, from 4-5 for C20:0, 3-4 for C22:0, and 2 for C24:0; we validated our previous conclusion that BSA has only one site for C26:0 (Ho, J. K., H. Moser, Y. Kishimoto, and J. A. Hamilton. 1995. J. Clin. Invest. 96: 1455-1463). Analysis of chemical shifts suggested that the highest affinity sites for VLCFA are low affinity sites for long-chain fatty acids. In competition experiments with C-13-labeled C22:0 (3 mol/ mol of BSA) and unlabeled oleic acid, C22:0 bound to BSA in the presence of up to 4 mol of oleic acid/mol of BSA, but I mol was shifted into a different site. Our studies suggest that albumin has adequate binding capacity for the low plasma levels of VLCFA with 20 to 26 carbons, but the protein may not be able to bind longer chain VLCFA.