Isolation of Inactive Renin from Human Plasma and Its Activation by Proteolytic Enzymes

A completely inactive renin was isolated from normal human plasma by DEAE-Sepharose column chromatography, 70% ammonium sulfate precipitation and Blue-Sepharose column chromatography. This preparation had a specific activity of 122 ng ANG I/mg protein/h, when activated by trypsin. The inactive renin had an apparent molecular weight of 54,000 daltons as determined by gel filtration on Ultrogel AcA 44. Homogeneous human kidney renin (2.4 ng/100 micrograms of the inactive renin) activated the inactive renin. Trypsin (2 micrograms), highly purified human plasmin (70 micrograms) and homogeneous human plasma kallikrein (130 micrograms) activated the inactive renin by 100%, by 75% and by 17%, respectively. But highly purified human urinary kallikrein (up to 150 micrograms) did not activate the inactive renin at all. Trypsin-activated renin was a little different from natural plasma active renin with respect to molecular and kinetic properties. When the trypsin-activated renin was treated with human urinary kallikrein, its activity was unchanged, but its molecular weight, Km value, Ki value of pepstatin A and pH profile became identical with those of plasma active renin. On the other hand, renin-activated renin had the same kinetic properties of plasma active renin and human kidney renin, but had the same molecular weight (38,000) as human kidney renin that was smaller than natural plasma active renin (43,000).