PDF(Pubmed)
Abstract：
The enzymatic activity of the aspartic protease, renin, is critical for its function in blood pressure regulation and sodium homeostasis. Incubation of so-called native prorenin at low pH leads to its activation. After binding to transition-state mimicking renin inhibitors at neutral pH, prorenin attains the active conformation, as indicated by immunosorbent assay using monoclonal antibodies specific for epitopes of the prosegment or the renin body. A comparison of immunosorbent assay with enzyme-kinetic assay revealed the intermediary steps of prorenin auto-activation/inactivation. The kinetically identified intermediary steps of activation/inactivation correspond with the published crystal structures of free renin, free prorenin, and renin in complex with inhibitors. Both renin and activated prorenin exist in 2 forms, α and β. The α form is active, and the α/β quantity ratio is 2.5. The kidney produces renin and prorenin, while the ovarium, placenta, and eye produce inactive prorenin. The production of renin by these organs has never been demonstrated. We propose that the so-called native prorenin in extracellular fluid, including the circulation, is derived, at least partly, from short-lived active prorenin. Its potential paracrine function is discussed.
摘要：
天冬氨酸蛋白酶的酶活性，肾素,对其在血压调节和钠稳态中的功能至关重要。在低pH下孵育所谓的天然肾素原导致其活化。在中性pH下与过渡态模拟肾素抑制剂结合后，肾素保持活性构象，如使用对前段或肾素体的表位具有特异性的单克隆抗体的免疫吸附测定所指示的。免疫吸附测定与酶动力学测定的比较揭示了肾素原自动激活/失活的中间步骤。动力学确定的激活/失活的中间步骤与已发表的游离肾素的晶体结构相对应，游离的肾素,和肾素与抑制剂复合。肾素和激活的肾素原都以两种形式存在，α和β。α形式是活跃的，α/β数量比为2.5。肾脏产生肾素和肾素原,而卵巢，胎盘,眼睛产生不活跃的肾素原。从未证明这些器官产生肾素。我们认为细胞外液中所谓的天然肾素原，包括流通，是派生的，至少部分地,来自短命的活性肾素原。讨论了其潜在的旁分泌功能。
