SOME LIPID-PROTEIN INTERACTIONS INVOLVED IN PROTHROMBIN ACTIVATION

1. 1. Bovine plasma prothrombin forms a macromolecular complex with an equimolar mixture of phosphatidylserine and phosphatidylcholine in aqueous dispersion. Complex formation, as detected by gel filtration on columns of Sephadex G-200, occurs only in the presence of an optimal concentration of Ca2+. 2. 2. Thrombin, bovine plasma albumin and an α1-acid glycoprotein are not adsorbed by the lipid particles either in the presence or absence of Ca2+. 3. 3. At-1°, prothrombin becomes attached to the particulate prothrombin activator complex consisting of activated factor X, factor V, phosphatidylserine/phosphatidylcholine mixture and Ca2+. At 37° in this system, prothrombin is converted to thrombin which itself is not adsorbed by the lipoprotein complex. 4. 4. The kinetics of prothrombin activation are consistent with a model involving catalysis of the reaction at the lipid-water interface and subsequent release of thrombin into the aqueous phase. Such a mechanism would favour the forward reaction by removing the reaction products from the site of their formation, at the same time creating sites for the renewed adsorption of prothrombin. © 1969.