Sequence Theories of Blood Coagulation re-evaluated with reference to Lipid-Protein Interactions

THE well-known “sequence” theories of blood coagulation 1,2 attempt to rationalize the participation of a dozen or so clotting factors in the formation, and consolidation of a fibrin clot. It has been proposed 3 that “normal prothrombin activation involves a number of functionally and perhaps physically distinct entities (clotting factors) present in the plasma, that these react one upon the other in a preferential sequence during normal clotting and that most, if not all, are proenzymes each yielding an enzyme capable of activating the next component of the sequence”. Several investigations have been concerned with the last of these propositions 4–11 . Each of these has involved the assumption that a linear response in reaction velocity with changing concentration is indicative of an enzyme while a saturation response is indicative of a substrate. The validity of these assumptions and their consequences will now be considered.