1. Purified inactive renin from human kidney or plasma was activated to a similar extent by incubation with trypsin or by dialysis to pH 3.3.
2. Trypsin- or acid-activated inactive renin was like active renal renin in terms of pH optimum (pH 5.5-6.0) and inhibition by mono-specific antibody. The apparent Km of homologous angiotensinogen for acid-activated inactive renin (1.11 μmol/l) was the same as for trypsin-activated inactive renin (1.12 μmol/l) or active renal renin (1.07 μmol/l).
3. In contrast with trypsin-activated renin, acid-activated renin was reversibly inactivated in a time-dependent manner during incubation at 37°C above pH 5. The maximal rate of reversal occurred in the pH 7–8 range. Reversal was prevented by prior incubation with trypsin, plasmin, glandular kallikrein or plasma kallikrein.
4. By kinetic analysis, the reversal of activation was found to be a first-order decay process with a reaction half-time (7–8 min at 37°C, pH 7.4) that was independent of the initial concentration of activated enzyme.
5. These results indicate that reversible acid-activation of inactive renin is a unimolecular reaction, consistent with the hypothesis that acid pH induces a conformational change in a single polypeptide chain.