Heparin reaction with proteins

J2. Jaques, L. B., The reaction of heparin with proteins and complex bases. Biochem. J. 37, 189-195 (1943). 

The subject of the present review stems from the discoveries of A. Fischer and E. Jorpes. Fischer demonstrated that heparin binds or complexes with proteins and other bases and so modifies their biological activity. As a result, heparin is able to release or activate enzymes such as lipoprotein lipase -, to inhibit hormones such as cortisone and aldosterone , to detoxify toxic agents, and to bind histamine in body cells . Jorpes discovered that heparin is a highly sulphated polysaccharide and that it gives a specific colour reaction with dyes the metachromatic reaction. This resulted in (i) the association of heparin with the naturally occurring mucopolysaccharides ... 

Heparinoids and mucopolysaccharides react with, and modify, many of the plasma proteins. Heparin combines with fibrinogen, globulins and albumin. As judged by electrophoresis and various types of analysis and staining, the particular plasma protein components with which heparin combines are dependent upon the concentration of protein, concentration of heparin, pH value, and salts present. This explains the somewhat contradictory statements in literature about combinations of heparin with plasma proteins. The combination may result in change of solubility of the protein and reverse protein tests . Heparin can modify the murexide reaction for calcium in serum by affecting the calcium-protein-heparin complex. Many heparinoids... 

Unfortunately, many investigations of the reaction between fibrinogen and thrombin have been carried out in whole plasma, with modification of the normal clotting process by the addition of heparin or oxalate, for example. The presence of such materials is an unnecessary complication, and in plasma it may be expected that other specific substances normally present, such as antithrombin, may also complicate the process. For unambiguous results, it is desirable to study the reaction with purified preparations of known fibrinogen content and thrombin activity, respectively, and in which any additional protein present is inert with respect to the clotting process. 

The kinetics of the lytic effect displayed by the complexes of immobilized heparin with thrombin and fibrinogen, in distinction from those with plasmin, are described by their saturation curves. The observed slowing down of the dissolution of unstabilized fibrin is probably due to the inhibiton of the lytic activity of the complexes by the soluble products of the reaction. In fact, as it was shown in Ref. 106, further addition of immobilized heparin-protein complex to partially hydrolyzed fibrin results in a complete recovery of the dissolution rate. 

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