The effects of pH on the generation of turbidity and elasticity associated with fibrinogen-fibrin conversion by thrombin are remarkably influenced by sialic acid in fibrinogen.
In fibrinogen-fibrin conversion by thrombin, the polymerization of a fibrin monomer is accompanied by gelation and an increase turbidity. Since sialic acids at the terminal of the carbohydrate chains bound to fibrinogen are part of the low affinity calcium binding site necessary for polymerization, they are closely involved in the network structure of fibrin clots. Fibrin clots derived from asialofibrinogen exhibited definite differences in turbidity and elasticity compared with those derived from intact fibrinogen, and were markedly dependent on the pH during the reaction. The turbidity during polymerization of fibrin, evaluated according to the absorbance at 350 nm, was maximum at pH 6.5-7.0, but it decreased in the other pH ranges, with the changes being unremarkable at higher pH levels but remarkable at lower pH ranges. The turbidity of fibrin derived from asialofibrinogen was far higher than that from intact fibrinogen near neutrality, but decreased rapidly and was lower than in intact fibrinogen at higher and lower pH ranges. Concerning the elasticity evaluated by thromboelastography, the coagulation time (k) and the maximum amplitude (ma) were lower in asialofibrinogen, indicating a deterioration of the clotting function of fibrinogen with the loss of sialic acid. These results suggest that sialic acid bound to fibrinogen is closely related to the fibrin network formation in blood coagulation, which is the most important function of fibrinogen, and plays a functional role in the stabilization of fibrin clot formation against environmental changes, including pH.
Okude
M
M
First Department of Biochemistry, Meiji College of Pharmacy, Tokyo, Japan.
Yamanaka
A
A
Akihama
S
S
D001212:Asialoglycoproteins / Q000502:physiology; D001777:Blood Coagulation; D004548:Elasticity; D005337:Fibrin / Q000378:metabolism*; D005340:Fibrinogen / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D019158:N-Acetylneuraminic Acid; D009391:Nephelometry and Turbidimetry; D012794:Sialic Acids / Q000378:metabolism*; D013917:Thrombin / Q000502:physiology*
D001212:Asialoglycoproteins; D012794:Sialic Acids; C032692:asialofibrinogen; D005337:Fibrin; D005340:Fibrinogen; D013917:Thrombin; D019158:N-Acetylneuraminic Acid