Inhibition of prothrombinase complex by plasma proteinase inhibitors.
The rate of inactivation of human coagulation factor Xa by the plasma proteinase inhibitors antithrombin III and alpha 1-antitrypsin has been studied in the presence of the accessory components which constitute the prothrombinase complex. The rate of inactivation of factor Xa by antithrombin III was found to be decreased in the presence of phospholipid vesicles with high affinity for factor Xa. The second-order rate constant for the reaction fell from 6.21 X 10(4) to 3.40 X 10(4) M-1 min-1 in the presence of 20 microM phospholipid. Purified factor Va had no effect on the rate of inactivation of factor Xa in the absence of phospholipid. In the presence of phospholipid, factor Va increased the protective effect displayed by phospholipid, further reducing the rate constant to 2.20 X 10(4) M-1 min-1. The rate of inactivation of factor Xa by alpha 1-antitrypsin was unaffected under these conditions. Platelet-bound prothrombinase complex was formed by incubation of factor Xa with washed human platelets activated by a mixture of collagen and thrombin. The prothrombinase activity was inhibited by antithrombin III was a second-order rate constant of 0.85 X 10(4) M-1 min-1. This rate was obtained in both the presence and absence of exogenous factor Va. Platelet factor 3 vesicles, isolated from platelet aggregation supernatants, also formed prothrombinase complex in the presence of factor Va, and this was inhibited by antithrombin III at the same rate as the platelet-bound complex. There was no protection of the platelet-bound prothrombinase complex from inhibition by alpha 1-antitrypsin.
D000818:Animals; D000990:Antithrombin III / Q000494:pharmacology*; D001792:Blood Platelets / Q000201:enzymology; D002417:Cattle; D005165:Factor V / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology; D015943:Factor Va; D005170:Factor X / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015951:Factor Xa; D006801:Humans; D007700:Kinetics; D008081:Liposomes / Q000378:metabolism; D010713:Phosphatidylcholines / Q000378:metabolism; D010718:Phosphatidylserines / Q000378:metabolism; D000515:alpha 1-Antitrypsin / Q000494:pharmacology*
D008081:Liposomes; D010713:Phosphatidylcholines; D010718:Phosphatidylserines; D000515:alpha 1-Antitrypsin; C022475:prothrombinase complex; D015943:Factor Va; D000990:Antithrombin III; D005165:Factor V; D005170:Factor X; D015951:Factor Xa