Anion-specific Effects on the Streptokinase Activation of Human Plasminogen

Abstract

Abstract Bicarbonate buffer was found to slow down the rate of human plasminogen activation by streptokinase. Increasing the pH of the activation medium from 7 to 10 or increasing the bicarbonate concentration to 0.3 m not only slowed down the rate of activation, but also gradually transformed the normally first order kinetics to a sigmoid pattern of development. The use of borate, instead of bicarbonate, buffer in the same pH and concentration range produced only insignificant changes in the rate of activation. The pH dependence of the bicarbonate effect suggests that the active ionic species is probably carbonate, rather than bicarbonate. The sigmoid pattern of development is interpreted as resulting from a decrease in the rate of formation of activator, a hypothetical streptokinase-proactivator complex, thought to be responsible for the catalytic conversion of plasminogen to plasmin. The use of bicarbonate permitted the detection of the process of activator formation separately from that of activator action, thereby lending support to the activator theory of human plasminogen activation by streptokinase. It is also observed that the pH profile of the proteolytic action of plasmin is markedly affected by bicarbonate. In addition, it is shown that, contrary to prevailing notions, e-aminocaproic acid does not prevent completely plasminogen activation by streptokinase, when measured by the casein assay. In the presence of bicarbonate, however, this inhibition is complete.