Urokinase에 의한 plasminogen 활성화 반응은 urokinase-plasminogen 복합체인 acyl-중간체를 경유하는 것으로 믿어지며, urokinase 분자내 활성화 부위 작용기로서는 histidine imidazole 잔기와 serine hydroxyl가 각각 염기성 및 천핵성 촉매제로서 작용, plasminogen의 활성화 반응에 참여될 수 있음을 pH 변화에 따른 반응 속도론적 실험과 착용기에 대한 화학적 불활성화 실험을 통하여 입증할 수 있었다. 아울러 본 연구결과를 토대로 하여 urokinase에 의하여 유도되는 plasminogen 활성화 반응에 대한 3단계 반응 메카니즘도 구상 검토해 보았다.
In order to elucidate the mechanism of the urokinase- induced plasminogen activetion, catalytically active functional groups which involved in the active site of urokinase molecule were investigated by a series of kinetic and chemical modification experiments. Inhibition study with several lysine and arginine derivatives indicates there involves hydrophobic interaction between urokinase and plasminogen molecules. 6-Amino hexanoic acid shows an exceptional high degree inhibition. The results from a set of pH-activity profiles and several chamical modification experiments suggest there involve at lease one serine hydroxyl moiety and one histidine imidazole group in the active site of the activator urokinase for the catalytic conversion of plaminogen into plasmin. Based on the results obtained, a minimal three step mechanism of the UK-induced plasminogen activation process was proposed as a working model.
