Ivarsen R, Brodersen R
Institute of Medical Biochemistry, University of Aarhus, Denmark.
Dev Pharmacol Ther. 1989;12(1):19-29.
Competitive binding of bilirubin and 5-butyl-1-cyclohexylbarbituric acid (bucolome) to human serum albumin was investigated by equilibrium dialysis, with and without added bilirubin (0.5 mol/mol albumin). Further observations were made by peroxidase oxidation kinetics. Finally, cobinding of the two ligands was studied by spectrophotometry. Experiments were performed with defatted adult human serum albumin, with umbilical cord serum, and with adult albumin to which was bound 2 mol palmitate/mol albumin. Bucolome does not induce displacement of bilirubin from binding to defatted adult albumin when one molecule of either ligand is bound. The second molecule of bound bucolome displaces the first bilirubin molecule. With albumin in umbilical cord serum, the first bucolome does decrease binding of the first bilirubin to some extent although the two ligands can bind to the same albumin molecule. The presence of two molecules of bound palmitate together with one of bilirubin causes enhanced bilirubin displacement on binding of bucolome. These observations may be of consequence for practical testing of the bilirubin displacing effect of drugs. Experiments with neonatal albumin and with added fatty acid should be included for a complete study.
通过平衡透析研究了胆红素与5-丁基-1-环己基巴比妥酸（布可隆）对人血清白蛋白的竞争性结合，分别在添加胆红素（0.5摩尔/摩尔白蛋白）和未添加胆红素的情况下进行。通过过氧化物酶氧化动力学进行了进一步观察。最后，通过分光光度法研究了两种配体的共结合。使用脱脂成人血清白蛋白、脐带血清以及每摩尔白蛋白结合2摩尔棕榈酸酯的成人白蛋白进行了实验。当任一配体结合一个分子时，布可隆不会诱导胆红素从与脱脂成人白蛋白的结合中被置换出来。结合的布可隆的第二个分子会置换第一个胆红素分子。对于脐带血清中的白蛋白，尽管两种配体可以结合到同一个白蛋白分子上，但第一个布可隆确实会在一定程度上降低第一个胆红素的结合。两个结合的棕榈酸酯分子与一个胆红素分子同时存在会导致在布可隆结合时胆红素置换增强。这些观察结果可能对药物胆红素置换作用的实际测试具有重要意义。为了进行完整的研究，应包括使用新生儿白蛋白和添加脂肪酸的实验。
