Studies of the plasmin system. II. Inhibition of plasmin by serum or plasma.

The inactivation of purified plasmin by serum or plasma was studied using a caseinolytic assay for determination of plasmin. On the basis of kinetic evidence, the presence of two inhibitors in normal human or guinea pig serum or plasma is suggested. The first reacts immediately at any temperature, but is easily dissociable and does not combine with plasmin in a fixed ratio. The second combines more slowly with plasmin at a rate which depends on temperature and on the concentration of both plasmin and inhibitor. There is a fixed ratio of reaction between plasmin and the second inhibitor and the combination does not readily dissociate. There is sufficient of the "slow" inhibitor in normal plasma to inactivate more than 30 times its own content of potential plasmin. The presence of suitable substrate for plasmin tends to reverse the combination with "immediate" inhibitor and to stop the further action of "slow" inhibitor.