Copper ion binding and heparin interactions of human fibrinogen.

Abstract

AbstractThe binding of copper ions to fibrinogen was studied by the equilibrium dialysis technique in neutral Tris buffer. The presence of copper causes precipitation of fibrinogen‐copper complexes, the amount of which varies with the copper ion concentration. Solutions of 96% clottable fibrinogen (whole fibrinogen) displayed a maximum binding capacity about four times greater than that of fibrinogen solutions from which the cold‐insoluble precipitate had been removed (cold‐soluble fibrinogen). Binding in both systems apparently involves two classes of sites in fibrinogen, and the class of lower affinity is associated with cooperative interactions with copper. The copper concentration at which this cooperative uptake occurs is identical to the concentration at which the amount of precipitated material increases sharply and also to the concentration at which a sharp decrease is observed in the sedimentation coefficient of soluble fibrinogen, suggesting some relationship between copper binding, solubility, and solution properties.The presence of heparin markedly affects the sedimentation coefficient of fibrinogen in the presence of copper ions, although showing a lesser effect in the absence of the metal. The sedimentation coefficient of fibrinogen is increased in the presence of heparin and copper ion, compared to the value of fibrinogen‐copper systems without heparin, and this effect is enhanced by changing the fibrinogen:heparin molar ratio to larger values. The precipitation of fibrinogen from solution, apparently without a coincident removal of heparin, also increases with increasing copper ion concentration and fibrinogen:heparin molar ratio. The possible significance of these effects in terms of heparin anti‐coagulant activity is discussed.