Fatty acid binding proteins from different tissues show distinct patterns of fatty acid interactions
Fatty acid binding proteins from different tissues show distinct patterns of fatty acid interactions
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DOI：
10.1021/bi000314z
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发表时间：
2000-06-20
期刊：
影响因子：
2.9
通讯作者：
Kleinfeld, AM
中科院分区：
文献类型：
--
作者：
Richieri, GV;Ogata, RT;Kleinfeld, AM
脂肪酸结合蛋白(FABP)是一类具有组织特异性表达的蛋白质家族。这些蛋白质参与脂肪酸(FA)的运输和代谢，其机制似乎也是组织特有的，细胞维甲酸结合蛋白是相关蛋白质，在FA运输和代谢中的作用尚不清楚。为了更好地理解这些组织特异性差异的根源，我们报告了使用丙烯酰化肠道脂肪酸结合蛋白(ADIFAB)方法对来自大脑、心脏、肠道、肝脏和髓鞘的脂肪酸(FA)与人类脂肪酸结合蛋白(FABP)的结合进行新的测量。我们还测量了FA与维甲酸(CRABP-I)和视黄醇(CRBP-II)结合蛋白的结合，并将我们对FA-ADIFAB和FA-大鼠肠道FABP相互作用的表征扩展到19种不同的FA。这些研究扩展了我们之前对脂肪细胞的人FABP和来自心脏、肠道和肝脏的大鼠FABP的分析。结合亲和力按脑髓磷脂近似心、肝、肠、CRABP、CRBP、CRBP的顺序变化。与以前的研究相比，没有任何蛋白质显示出对特定FA的高度选择性。结果表明，FA的疏水性(疏水性)在控制结合亲和力方面起主要作用；亲和力随着FA疏水性(溶解性的降低)的增加而增加。然而，我们的结果也显示，除了肠道蛋白外，FABP对不饱和脂肪酸表现出额外的有吸引力的相互作用，这部分补偿了它们由于较高的水溶解度而导致亲和力降低的趋势。测定了油酸和花生四烯酸与部分FABP和维甲酸结合蛋白的热力学势能。FA与所有FABP的结合都是由热能驱动的。来自同一物种但不同组织的同源FABP的Delta H度值显示出异常广泛的值，从-22千卡/摩尔(髓鞘)到-7千卡/摩尔(脂肪细胞)。来自同一组织不同物种的同源FABP的Delta H度值相似。与FA与FABP结合的焓优势相反，FA与CRABP-I的结合是熵驱动的，这与FA对FABP的专一性由结合热决定的观点是一致的。来自不同组织的蛋白质在FA结合时的热容变化也表现出相当大的异质性，Delta C-p值在0到-1.3kcal摩尔(-1)K-1之间。结果表明，近亲动物的热力学参数有很大的不同，但同源FABP的热力学参数非常相似，这表明FABP功能的组织特异性差异可能在不同物种之间保持不同。
Fatty acid binding proteins (FABP) form a family of proteins displaying tissue-specific expression. These proteins are involved in fatty acid (FA) transport and metabolism by mechanisms that also appear to be tissue-specific, Cellular retinoid binding proteins are related proteins with unknown roles in FA transport and metabolism. To better understand the origin of these tissue-specific differences we report new measurements, using the acrylodated intestinal fatty acid binding protein (ADIFAB) method, of the binding of fatty acids (FA) to human fatty acid binding proteins (FABP) from brain, heart, intestine, liver, and myelin. We also measured binding of FA to a retinoic acid (CRABP-I) and a retinol (CRBP-II) binding protein and we have extended to 19 different FA our characterization of the FA-ADIFAB and FA-rat intestinal FABP interactions. These studies extend our previous analyses of human FABP from adipocyte and rat FABPs from heart, intestine, and liver. Binding affinities varied according to the order brain approximate to myelin approximate to heart > liver > intestine > CRABP > CRBP. In contrast to previous studies, no protein revealed a high degree of selectivity for particular FA. The results indicate that FA solubility (hydrophobicity) plays a major role in governing binding affinities; affinities tend to increase with increasing hydrophobicity (decreasing solubility) of the FA. However, our results also reveal that, with the exception of the intestinal protein, FABPs exhibit an additional attractive interaction for unsaturated FA that partially compensates for their trend toward lower affinities due to their higher aqueous solubilities. Thermodynamic potentials were determined for oleate and arachidonate binding to a subset of the FABP and retinoid binding proteins. FA binding to all FABPs was enthalpically driven. The Delta H degrees values for paralogous FABPs, proteins from the same species but different tissues, reveal an exceptionally wide range of values, from -22 kcal/mol (myelin) to -7 kcal/mol (adipocyte). For orthologous FABPs from the same tissue but different species, Delta H degrees values were similar. In contrast to the enthalpic dominance of FA binding to FABP, binding of FA to CRABP-I was entropically driven, This is consistent with the notion that FA specificity for FABP is determined by the enthalpy of binding. Proteins from different tissues also revealed considerable heterogeneity in heat capacity changes upon FA binding, Delta C-p values ranged between 0 and -1.3 kcal mol(-1) K-1. The results demonstrate that thermodynamic parameters are quite different for paralogous but are quite similar for orthologous FABP, suggesting tissue-specific differences in FABP function that may be conserved across species.