A large form of renin from normal human kidney.

The apparent molecular size of circulating human plasma renin is 43,000 daltons. In this report, the Stokes' radius of renin extracted from human kidney cortex in low ionic strength buffer in the presence of protease inhibitors was shown to correspond to an apparent molecular weight of 58,000 +/- 3,000. If protease inhibitors are omitted, if the kidney tissue is frozen and thawed multiple times, or if the kidney extract is acidified to pH 2.8, renin activity of an apparent molecular size of 42,000 +/- 3,000 can be identified. Both species of renin bind to an affinity support bearing the substrate analog inhibitor His-Pro-Phe-His-Leu-D-Leu-Val-Tyr. Antibody raised to the higher molecular form of the enzyme inhibits the activity of both forms in an equivalent manner. These observations suggest that the larger form of renin may be a biosynthetic precursor of plasma renin, either in the form of a zymogen or an enzyme-binding protein complex.