Institute for the Application of Nuclear Energy (INEP), Department for Metabolism, University of Belgrade, Banatska 31b, 11000 Belgrade, Serbia.
Institute of Chemistry, Technology and Metallurgy, University of Belgrade, Njegoševa 12, 11000 Belgrade, Serbia.
Int J Biol Macromol. 2020 Mar 15;147:319-325. doi: 10.1016/j.ijbiomac.2020.01.098. Epub 2020 Jan 10.
A reduced form of the alpha-lipoic acid, dihydro-alpha-lipoic acid (DHLA) is a potent, naturally occurring antioxidant which can be consumed as food constituent or as supplement at doses up to 600 mg/day. DHLA has inhibitory effect on coagulation as it can reduce concentrations of some coagulation factors. In this study, a direct interaction between DHLA and fibrinogen, the main protein in coagulation, is described. Binding constant for DHLA/fibrinogen complex is of moderate strength (10) and interaction probably occurs in D regions of fibrinogen, as shown by docking simulations. Fibrinogen stability remains the same with only marginal structural changes in its secondary structure favouring more ordered molecular organisation upon DHLA binding. Fibrinogen with bound DHLA forms fibrin with thicker fibers, as measured by coagulation assay and is protected from oxidation to certain extent. Obtained results support beneficial effects of DHLA on fibrinogen and consequently on coagulation process, suggesting that DHLA supplementation may be indicated for persons with an increased risk of developing thrombotic complications, particularly those whose fibrin is characterised by increased oxidative modification and formation of thinner and less porous fibers. Also, DHLA in complex with fibrinogen can be located at site of injury where it may exert antioxidant effects.
二氢硫辛酸（DHLA）是一种天然存在的、具有很强抗氧化作用的α-硫辛酸的还原形式，可以作为食物成分或补充剂摄入，每天剂量高达 600mg。DHLA 可以通过降低某些凝血因子的浓度来抑制凝血。本研究描述了 DHLA 与纤维蛋白原（凝血的主要蛋白质）之间的直接相互作用。DHLA/纤维蛋白原复合物的结合常数具有中等强度（10），并且可能发生在纤维蛋白原的 D 区，这是通过对接模拟显示的。纤维蛋白原的稳定性保持不变，其二级结构只有微小的结构变化，有利于 DHLA 结合后更有序的分子组织。与 DHLA 结合的纤维蛋白原形成的纤维蛋白，其纤维更厚，如通过凝血测定测量的那样，并且在一定程度上受到氧化保护。所得结果支持 DHLA 对纤维蛋白原的有益作用，进而对凝血过程产生有益作用，这表明 DHLA 补充剂可能适用于有发生血栓并发症风险增加的人，特别是那些纤维蛋白以增加的氧化修饰和形成更细和更不透气的纤维为特征的人。此外，与纤维蛋白原结合的 DHLA 可以位于损伤部位，在那里它可以发挥抗氧化作用。
