Platelet Membrane Lipid Acts to Promote Blood Clotting

A new study has revealed that the lipid phosphatidylserine (PS) plays a crucial role in the conversion of prothrombin to thrombin, which is the final step in the process of blood coagulation. The study appeared in the June 3, 2002, online edition of the Journal of Biological Chemistry and in the August 2002 printed edition.

Factor Xa (FXa) binding to factor Va (FVa) on platelet-derived membranes containing surface-exposed phosphatidylserine (PS) forms the "prothrombinase complex” that is essential for efficient thrombin generation during blood coagulation. There are two naturally occurring isoforms of Fva: FVa1 and FVa2. These two isoforms differ by a three KDalton polysaccharide chain and have different coagulant activities.

A soluble form of PS (C6PS) was found to bind to FVa1 and FVa2 with comparable affinities and changes in FVa intrinsic fluorescence. At concentrations well below its critical micelle concentration, C6PS binding to bovine FVa2 enhanced its affinity for FXa in solution by nearly three orders of magnitude but had no effect on the affinity of FVa1 for FXa. This resulted in a soluble complex between FXa and FVa2, whose expected molecular weight was confirmed by calibrated native gel electrophoresis. This complex behaved as a normal Michaelis-Menten enzyme in its ability to produce thrombin from meizothrombin. The ability of soluble PS to trigger formation of a soluble prothrombinase complex suggested that exposure of PS molecules during platelet activation is likely the key event responsible for the assembly of an active membrane-bound complex.

Dr. Barry R. Lentz, professor of biochemistry and biophysics at the University of North Carolina School of Medicine (Chapel Hill, USA) and senior author, said that the findings unequivocally supported a new view, that PS can activate conversion of prothrombin to thrombin in the absence of the platelet membrane surface. It does so by triggering assembly of the enzyme complex, prothrombinase, which is crucial to that process.

Dr. Lentz added, "If you want to control blood coagulation--either to promote it or to diminish it in a setting where you do not want clots to form--the binding sites for phosphatidylserine may be good targets for drug design.”



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