BioResearch Lab, Faculty of Biological Sciences, Shahid Beheshti University, G.C., Iran.
Department of Pharmacology & Toxicology, Pharmaceutical Sciences Branch, Islamic Azad University (IAUPS), Tehran, Iran.
Int J Biol Macromol. 2017 Jan;94(Pt B):788-792. doi: 10.1016/j.ijbiomac.2016.09.049. Epub 2016 Sep 16.
After red blood cells lysis, hemoglobin is released to blood circulation. Hemoglobin is carried in blood by binding to haptoglobin. In normal individuals, no free hemoglobin is observed in the blood, because most of the hemoglobin is in the form of haptoglobin complex. In some diseases that are accompanied by hemolysis, the amount of released hemoglobin is higher than its complementary haptoglobin. As a result, free hemoglobin appears in the blood, which is a toxic compound for these patients and may cause renal failure, hypertensive response and risk of atherogenesis. Free hemoglobin has been determined to have peroxidase activity and considered a pseudoenzyme. In this study, the effect of methocarbamol on the peroxidase activity of human hemoglobin was investigated. Our results showed that the drug inhibited the pseudoenzyme by un-competitive inhibition. Both K and V decreased by increasing the drug concentration. K and IC values were determined as 6 and 10mM, respectively. Docking results demonstrated that methocarbamol did not attach to heme group directly. A hydrogen bond linked NH of carbamate group of methocarbamol to the carboxyl group of Asp126 side chain. Two other hydrogen bonds could be also observed between hydroxyl group of the drug and Ser102 and Ser133 residues of the pseudoenzyme.
红细胞溶解后，血红蛋白释放到血液循环中。血红蛋白通过与触珠蛋白结合在血液中运输。在正常个体中，血液中观察不到游离的血红蛋白，因为大部分血红蛋白以触珠蛋白复合物的形式存在。在一些伴有溶血的疾病中，释放的血红蛋白量高于其互补的触珠蛋白。因此，游离的血红蛋白出现在血液中，这对这些患者是一种有毒的化合物，可能导致肾衰竭、高血压反应和动脉粥样形成的风险。游离血红蛋白已被确定具有过氧化物酶活性，并被认为是一种伪酶。在这项研究中，研究了 methocarbamol 对人血红蛋白过氧化物酶活性的影响。我们的结果表明，该药物通过非竞争性抑制抑制了伪酶。随着药物浓度的增加，K 和 V 均降低。K 和 IC 值分别确定为 6 和 10mM。对接结果表明，methocarbamol 并未直接与血红素基团结合。carbamate 基团的 NH 与 Asp126 侧链的羧基通过氢键连接。还可以观察到药物的两个羟基与伪酶的 Ser102 和 Ser133 残基之间的另外两个氢键。
