Purification and biochemical characterization of F II(a), a fibrinolytic enzyme from Agkistrodon acutus venom.

A fibrinolytic enzyme, F II(a), was isolated from Agkistrodon acutus venom by ion-exchange chromatography and gel filtration. F II(a) consisted of a single polypeptide chain with a molecular weight of 26,000 and an isoelectric point of 4.6. F II(a) was shown to solubilize fibrin and fibrinogen. F II(a) cleaved, primarily, the alpha chain of fibrinogen and fibrin followed by the beta chain, while the gamma chain was minimally affected. Thus, the enzyme was an alpha,beta-fibrinogenase. The cleavage pattern of fibrinogen clearly varied from plasmin cleavage of the same molecule. In vivo, F II(a) had no influence on the rat's tissue-type plasminogen activator and plasminogen activator inhibitor-1 activities in plasma. At the dosage of 5mg/kg, histological examination of heart, liver and lung tissue showed no hemorrhage. F II(a) is an enzyme that hydrolyzed fibrin directly without hemorrhagic activity.