Inactivation of human coagulation factor V by activated protein C.

Abstract

Thrombin-activated vitamin K-dependent protein C purified from human plasma has a potent anticoagulant effect on human plasma, whereas its bovine counterpart has a very weak anticoagulant effect on human plasma. This species difference was found to be partly due to a more rapid degradation of human factor Va by human than by bovine activated protein C. In the presence of phospholipid, activated human protein C cleaves several peptide bonds in fragment D (heavy chain of factor Va), whereas in fragment F1F2 (light chain of factor Va) there appears to be only one peptide bond that is slowly cleaved. The degradation of fragment D is accompanied by a parallel loss of factor V activity. With the blood coagulation factor Xa bound to factor Va, fragment D is protected from degradation by activated protein C, and factor Va remains active. Fragment D isolated from factor Va was exposed to activated protein C in the presence of phospholipid and was found not to be degraded. This observation suggests that fragment D of factor V is bound to phospholipid via fragment F1F2.