Influence of the Carbohydrate Moiety in the Dysfibrinogenemia of Liver Disease
Human fibrinogen is a glycoprotein which contains 6 sialic acid residues per molecule. Enzymatic removal of sialic acid modifies its functional properties as indicated by shortening of the thrombin time due to enhanced asialofibrin monomer polymerization. The abnormal fibrinogen of liver disease contains an Increased amount of sialic acid and is functionally characterized by impaired fibrin monomer polymerization. The prolongation of its thrombin time correlates with its increased sialic acid content. Enzymatic cleavage of the excess sialic acid results in normalization of the thrombin time and the fibrin monomer polymerization. Quantitative labelling of sialic acid with (3H) demonstrates increased labelling of the abnormal fibrinogen compared to normal fibrinogen reflecting the sialic acid content of the abnormal molecule. The radioactivity of the labelled normal and abnormal fibrinogens after reduction and SDS-PAGE was limited to the Bβ and γ chains with 60% of the radioactivity in the Bβ chain and 40% in the γ chain. A similar distribution of radioactivity was found after removal of the excess sialic acid from the respective chains. β-galactose was also increased in the abnormal fibrinogen and paralleled the increase in sialic acid. These studies indicate that sialic acid is distributed normally on the chains of the abnormal fibrinogen of liver disease, but its increased content is responsible for the functional defect of the protein.