The activation of human plasminogen by streptokinase.

Human plasma contains a proteolytic enzyme precursor termed plasminogen (I) or profibrinolysin (2), which, upon activation by physical agents or specific bacterial kinases, is converted to plasmin (1) or fibrinolysin (2). Streptokinase (henceforth referred to as SK), an extracellular hemolytic streptococcal product, has been a commonly used activator for human plasminogen. Two mechanisms have been proposed for the activation of plasminogen by SK: (a) plasminogen is converted to plasmin, a new substance, by enzymatic activation (3) and (b) the conversion of plasminogen to plasmin results from a “stoichiometric” interaction of SK with plasminogen (4, 5). Studies with synthetic substrates on the activation of plasminogen by SK reveal that human plasminogen preparations contain two factors: a proactivator, converted by SK in stoichiometric fashion to a plasminogen activator, and plasminogen, which is enzymatically converted by the activator to the proteolytic enzyme plasmin. Evidence for a two-step activation of plasminogen by SK, in agreement with that recently suggested by others (6, 7), was obtained through three types of studies: (a) fractionation experiments demonstrating two factors in SK-activated plasminogen preparations, i.e. a lysine esterase alone, and a proteolytic enzyme capable of splitting casein, arginine, and lysine esters; (b) inhibition experiments relating the lysine esterase to the plasminogen activator; and (c) activation experiments demonstrating the reversible stoichiometric activation of the lysine esterase by SK and the enzymatic activation of the proteolytic enzyme.