Institute for the Application of Nuclear Energy, Department for Metabolism, University of Belgrade, Banatska 31b, 11080 Belgrade, Serbia.
Faculty of Chemistry, Department of Biochemistry, Centre of Excellence for Molecular Food Sciences, University of Belgrade, Studentski trg 12-16, 11000 Belgrade, Serbia.
Int J Biol Macromol. 2019 May 1;128:74-79. doi: 10.1016/j.ijbiomac.2019.01.124. Epub 2019 Jan 23.
Fibrinogen, a protein involved in blood coagulation, is very susceptible to oxidation. Oxidation alters its function and usually makes it more thrombogenic. Bilirubin, an end-product of the haem degradation in vertebrates, is known for its antioxidant properties. The present paper describes interaction between fibrinogen and bilirubin, and the influence of bilirubin on the formation of fibrin and protection against oxidation. The binding constant of 4.5 × 10 M was determined for the fibrinogen/bilirubin complex at 37 °C. There is no change in secondary and tertiary structure of fibrinogen or its thermal stability upon bilirubin binding. The binding site of fibrinogen is not stereospecific for bilirubin and is able to accommodate both bilirubin conformers. A change in absorption maximum of bilirubin occurs upon its interaction with fibrinogen, suggesting an alteration in the conformation of bilirubin to the more cyclic one. Bilirubin exerts antioxidant effect on fibrinogen, preventing its carbonylation and aggregation. The presence of bilirubin induces the formation of fibrin with thicker fibres, as assessed by the coagulation assay. Fibrinogen and bilirubin interact at physiological concentrations, bilirubin may act as an antioxidant for fibrinogen and may modulate an important event in haemostasis, which altogether suggests possible physiological relevance of this interaction.
纤维蛋白原是一种参与血液凝固的蛋白质，非常容易氧化。氧化会改变其功能，通常使其更具血栓形成性。胆红素是脊椎动物血红素降解的终产物，以其抗氧化特性而闻名。本文描述了纤维蛋白原与胆红素之间的相互作用，以及胆红素对纤维蛋白形成和氧化保护的影响。在 37°C 下，确定纤维蛋白原/胆红素复合物的结合常数为 4.5×10^M。胆红素结合不会改变纤维蛋白原的二级和三级结构或其热稳定性。纤维蛋白原的结合位点对胆红素没有立体特异性，能够容纳两种胆红素构象。胆红素与纤维蛋白原相互作用时，其吸收最大值发生变化，表明胆红素的构象发生变化，更趋于环状。胆红素对纤维蛋白原发挥抗氧化作用，防止其羰基化和聚集。如通过凝血测定评估的那样，胆红素的存在会诱导更厚纤维的纤维蛋白形成。纤维蛋白原和胆红素在生理浓度下相互作用，胆红素可能作为纤维蛋白原的抗氧化剂，并可能调节止血中的重要事件，这表明这种相互作用可能具有潜在的生理相关性。
