Requirement of zymogen modification for activation of porcine plasminogen

In physiological salt solutions, porcine plasminogen is refractory to activation by urokinase or trypsin and to proteolysis at Lys77 by plasmin or trypsin. Plasminogen becomes a substrate for urokinase (at Arg560), plasmin (at Lys77), and trypsin (at both bonds) if chloride ion is removed or if 6-aminohexanoate (2.5 mmol/L) is added. Irrespective of salts, activation of des(1-77)plasminogen is as efficient as activation of des(kringle1-4)plasminogen and is inhibited 50% by 2.5 mmol/L 6-aminohexanoate. In solutions lacking chloride or containing 6-aminohexanoate, plasminogen, des(1-77)plasminogen, and des(kringle1-4)plasminogen show no tendency to saturate urokinase in physiologically relevant concentrations (10 mumol/L). The findings are interpreted as indicating that plasminogen requires modification, either by proteolysis or by ligands, for activation.