Koga D, Hayashi K
J Biochem. 1976 Mar;79(3):549-58. doi: 10.1093/oxfordjournals.jbchem.a131099.
The activation process of pepsinogen was analyzed by a combination of computer simulation and experiment. In order to investigate in detail the behavior of the basic schemes proposed in the previous study, further computer simulations were conducted. Some experiments were performed based on the information obtained. The changes in the UV difference spectrum in the early stage was measured by the stopped-flow technique and the conversion of pepsinogen to pepsin [EC 3.4.23.1] was followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Furthermore, on the basis of the experimental results, the most reasonable scheme was selected and modified. As a result, a scheme for the activation process of pepsinogen was obtained (Scheme 8). On the basis of the above analyses, it was assumed that the first step and the third step are pH-dependent based on the change in the UV spectrum, that the second step is a nonlinear reaction containing a looped reaction with a dimeric intermediate (in this step, peptide fragments are released and pepsinogen is converted to a pepsin-like molecule), and that the third step is an equilibrium reaction involving proton binding.
通过计算机模拟与实验相结合的方法分析了胃蛋白酶原的激活过程。为了详细研究先前研究中提出的基本方案的行为，进行了进一步的计算机模拟。基于所获得的信息进行了一些实验。采用停流技术测量早期紫外差光谱的变化，并通过十二烷基硫酸钠-聚丙烯酰胺凝胶电泳追踪胃蛋白酶原向胃蛋白酶[EC 3.4.23.1]的转化。此外，根据实验结果，选择并修改了最合理的方案。结果，获得了胃蛋白酶原激活过程的方案（方案8）。基于上述分析，根据紫外光谱的变化推测第一步和第三步是pH依赖性的，第二步是包含与二聚体中间体的环状反应的非线性反应（在这一步中，肽片段被释放，胃蛋白酶原转化为类胃蛋白酶分子），第三步是涉及质子结合的平衡反应。
