Prorenin and Other Large Molecular Weight Forms of Renin*

PRORENIN is a completely inactive form of renin that circulates in human plasma in concentrations close to 10 times that of active renin. A similar inactive form of renin appears to be secreted from the kidney, but an extrarenal source can also contribute to the plasma level. Prorenin should not be confused with large molecular weight forms of renal renin that have intrinsic enzymatic activity. These appear to be, at least in part, the result of binding of renin to a renal cortical protein. Plasma prorenin can be activated by the techniques of cryoactivation and acid activation. It can also be converted to active renin by neutral serine proteases such as trypsin, glandular kallikrein, plasma kallikrein, and plasmin, and by acid proteases such as pepsin and cathepsin D. Both cryoactivation and acid activation appear to be mediated, in part, by endogenous plasma kallikrein which converts prorenin to renin in plasma in vitro after either cold inactivation or acid destruction of plasma kallikrein inhibitors. Plasma prorenin is also partially activated below pH 4, perhaps by an endogenous acid protease.