Functional and metabolic properties of human asialofibrinogen.
The role of sialic acid in the functional and metabolic properties of purified human fibrinogen was investigated. Fibrinogen treated with Vibrio cholerae neuraminidase released 90 percent of its sialic acid without evidence of proteolysis, as indicated by the presence of intace A alpha, B beta, and gamma chains on sodium dodecylsulfate (SDS)-polyacrylamide gels of the reduced asialoprotein. The thrombin and Reptilase clotting times of human asialofibrinogen were shortened compared to those of normal fibrinogen. Fibrinopeptide release was normal in rate and amount, but asialofibrin monomer aggregation was increased at both low and high ionic strength. Similarly, the asialo-derivative of fibrinogen Philadelphia (functionally characterized by impairment of fibrin monomer aggregation) demonstrated shortening of its thrombin and Reptilase times and improvement in its monomer aggregation especially at high ionic strength. Asialofibrin showed a normal capacity to form cross-linked fibrin as demonstrated by normal gamma-chain dimerization and alpha-chain polymerization. Simultaneous metabolic studies of human normal fibrinogen and asialofibrinogen in rabbits revealed only a modest decrease in the half-life of the asialoprotein compared to the intact protein, with no preferential uptake of the asialo-derivative by the liver. Control studies with rabbit normal fibrinogen and asialofibrinogen in rabbits revealed the same modest difference in half-life. Thus, asialofibrinogen clots faster due to enhancement of its monomer aggregation, has a normal capacity to form cross-linked fibrin, and does not differ significantly in its metabolic properties from normal fibrinogen. The possible influence of sialic acid in the functional abnormality of some congenital dysfibrinogenemias is discussed.
D001780:Blood Coagulation Tests; D005337:Fibrin / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D012794:Sialic Acids / Q000502:physiology*
D012794:Sialic Acids; D005337:Fibrin; D005340:Fibrinogen