Concept of a Common Protein Moiety, Containing Disulfide Bonds, in Prothrombin, Prothrombin Derivative (Autoprothrombin) and Thrombin

¹ From the Department of Pathology, College of Medicine, State University of Iowa, Iowa City, Iowa

With a recently devised argentometric amperometric method, disulfide was demonstrated in biothrombin, citrate thrombin and prothrombin derivative (autoprothrombin) in the same quantity (43 µm/100 mg N) as that present in prothrombin. Sulfhydryl groups were not detected in any of these clotting factors. Prolonged storage and denaturation by heating before disulfide could be detected in some samples of thrombin, as well as a difference in sensitivity to the inhibitory effect of sulfhydryl compounds, indicate a distinction between prothrombin and thrombin in the accessibility of their —S—S— bonds. The prothrombin derivative (autoprothrombin) on which the sulfhydryl and disulfide analyses were performed was shown to be deficient in prothrombin and thrombin activity, to exhibit pronounced factor VII activity and to be capable of conversion to thrombin by sodium citrate, but not by biological activators. The inhibition, amperometric and activator studies provide additional support for a monophyletic hypothesis of a single, but complex, glycoprotein, which possesses a protein moiety containing—S—S—bonds, and which by alteration of its side chains or end groups, may exhibit prothrombin, thrombin or accelerator activity. Such studies render the possibility that factor VII is a specific protein entity, increasingly doubtful.