Inhibition of human blood coagulation factor Xa by .alpha.2-macroglobulin

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Abstract
The inactivation of activated factor X (factor Xa) by .alpha.2-macroglobulin (.alpha.2M) was studied. The second-order rate constant for the reaction was 1.4 .times. 103 M-1 s-1. The binding ratio was found to be 2 mol of factor Xa/mol of .alpha.2M. Interaction of factor Xa with .alpha.2M resulted in the appearance of four thiol groups per molecule of .alpha.2M. The apparent second-order rate constants for the appearance of thiol groups were dependent on the factor Xa concentration. Sodium dodecyl sulfate gradient polyacrylamide gel electrophoresis was used to study complex formation between .alpha.2M and factor Xa. Under nonreducing conditions, four factor Xa-.alpha.2M complexes were observed. Reduction of these complexes showed the formation of two new bands. One complex (Mr 225,000) consisted of the heavy chain of the factor Xa molecule covalently bound to a subunit of .alpha.2M, while the second complex (Mr 400,000) consisted of the heavy chain of factor Xa molecule and two subunits of .alpha.2M. Factor Xa was able to form a bridge between two subunits of .alpha.2M, either within one molecule of .alpha.2M or by linking two molecules of .alpha.2M. Complexes involving more than two molecules of .alpha.2M were not formed.

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