Biochemistry of Streptokinase

Abstract

Streptokinase (SK), an extracellular protein produced by various strains of streptococci, is capable of converting human plasminogen to plasmin. Its capacity to cause lysis of blood clots was first described by Tillet and Garner in 1933. This effect was thought to be due to direct enzymatic action on the fibrin of these clots. However, Milstone, in 1941, demonstrated that streptokinase achieved its effect through activation of a plasma protein. Thus the proenzyme and enzyme forms of this plasma protein were given the names plasminogen and plasmin, respectively, and the bacterial extract was given the name streptokinase. As of now, plasminogen and plasmin are the only substrates with which SK is known to react. Evidence indicates that a 1:1 molar complex of streptokinase and plasminogen or plasmin is formed producing an “activator complex” which then converts free (uncomplexed) plasminogen to plasmin. Activator activity may be defined in terms of its ability to convert bovine and guinea pig plasminogens to plasmin directly. Plasminogen, plasmin and streptokinase alone are unable to carry out this conversion. Activator is further characterized by its ability to cause lysis on unheated but not heated beef fibrin agar plates, the fact it is not inhibited by soy bean trypsin inhibitor, and its ability to convert guinea pig plasminogen to plasmin in the casein guinea pig serum assay.