Inactivation of human coagulation factor V by activated protein C.
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.
D000596:Amino Acids / Q000032:analysis; D001779:Blood Coagulation Factors / Q000502:physiology*; D004789:Enzyme Activation; D005165:Factor V / Q000502:physiology*; D015943:Factor Va; D005170:Factor X / Q000502:physiology; D015951:Factor Xa; D006023:Glycoproteins / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D008970:Molecular Weight; D011486:Protein C; D013917:Thrombin / Q000502:physiology
D000596:Amino Acids; D001779:Blood Coagulation Factors; D006023:Glycoproteins; D011486:Protein C; D015943:Factor Va; D005165:Factor V; D005170:Factor X; D013917:Thrombin; D015951:Factor Xa