Rijken D C, Emeis J J
Biochem J. 1986 Sep 15;238(3):643-6. doi: 10.1042/bj2380643.
In order to assess which part of the tissue-type plasminogen activator (t-PA) molecule should be (genetically) modified to obtain more-slowly-clearing mutants, two-chain t-PA and its isolated heavy and light chains were radiolabelled and injected into rats. The vast majority of t-PA and the heavy chain disappeared from the blood circulation with half-lives of 2.3 and 1.0 min respectively. The clearance of the light chain was biphasic, owing to complex-formation with plasma proteinase inhibitors. The disappearance of di-isopropylphospho-light chain, which has a blocked active site, was nearly monophasic, with a half-life of 5.7 min. Organ distribution studies showed that hepatic clearance constituted the major pathway in all cases. These results strongly suggest that t-PA is recognized by the liver primarily through the heavy chain.
为了评估组织型纤溶酶原激活剂（t-PA）分子的哪一部分应该（通过基因）改造以获得清除更慢的突变体，对双链t-PA及其分离的重链和轻链进行放射性标记，并注射到大鼠体内。绝大多数t-PA和重链分别以2.3分钟和1.0分钟的半衰期从血液循环中消失。轻链的清除是双相的，这是由于与血浆蛋白酶抑制剂形成复合物。具有封闭活性位点的二异丙基磷酸轻链的消失几乎是单相的，半衰期为5.7分钟。器官分布研究表明，在所有情况下，肝脏清除都是主要途径。这些结果有力地表明，肝脏主要通过重链识别t-PA。
