Lipoprotein lipases heparin binding

Heparin is an important anticoagulant. It binds with factors IX and XI, but its most important interaction is with plasma antithrombin III (discussed in Chapter 51). Heparin can also bind specifically to lipoprotein lipase present in capillary walls, causing a release of this enzyme into the circulation. 

Relevant heparin-binding enzymes not involved in the coagulation cascade are, for example, elastase, cathepsin G, superoxide dismutase, lipoprotein lipase and other lipases. The plasma clearing properties of heparin are associated with its binding to lipoprotein lipase and hepatic lipase when the enzymes are released from the surface of endothelial cells [11] and have been studied in view of a potential impact on the regulation of atherosclerosis. 

Pande, D., Mathur, M.P. 1990. Evidence for the presence of a lipoprotein lipase in bovine UHT milk and its ionic binding to heparin. J. Food Sci. Technol. 27, 382-384. 

The use of vacutainer tubes and heparin was shown to alter the determination of protein binding. Heparin was shown to decrease the plasma binding of certain drugs including phenytoin, propranolol, lidocaine, diazepam, quinidine, and verapamil. This is also an in vitro artifact attributable to continued ex vivo activity of the lipoprotein lipase enzyme and accumulation of fatty acids in the blood collection tube. 

Coagulation factors, lipoprotein lipases, steroid receptors, hormones, DNA binding proteins, interferon, protein syntheses factors HiTrap Heparin 17-0406-01 17-0407-01 5 x 1 ml 1 x 5 ml ATIII (bovine) 3 mg/ml... 

VAN Tilbeurgh, H., Roussel, A., La-LOUEL, J.M., and Cambiliau, C. lipoprotein lipase. Molecular model based on the pancreatic lipase x-ray structure consequences for heparin binding and catalysis. J. Biol. Chem., 1994, 269, 4626-4633. 

Sendak, R.A., Bensadoun, A. 1998. Identification of a heparin-binding domain in the distal carboxy-terminal region of lipoprotein lipase by site-directed mutagenesis. J. Lipid Res. 39 1310-1315. 

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 ... 

Study of heparin binding to thrombin, 56 low-density lipoproteins, lipoprotein lipase, circulatory serine proteases, proteinase inhibitors, heparin-binding growth factors, blood vessel-associated proteins (fibronectin and laminin) and binding to cells and tissues. Study of anticoagulant activity and the modulation of the structure, function and metabolism of many proteins and en-2ymes. 

Functions.—Heparin fractionated by gel filtration appeared to bind to two sites on antithrombin III (association constants 0.6 x 10 and 0.2 x 10 moll" ), whereas heparin prepared by affinity chromatography on matrix-bound antithrombin III appeared to bind to only one site (association constant 2.3 x 10 moll ). These results suggest that one of the binding sites on antithrombin III does not bind the most active heparin components, but accommodates heparin-like molecules which, although similar in size to the active heparin components, have little or no anticoagulant activity. Heparins with high or low affinities for antithrombin III exhibited no differences in their abilities to bind lipoprotein lipase. Studies of the interaction between the lipoprotein lipase from cow s milk and Sepharose-immobilized heparin have shown that heparin is poly-disperse. Whereas heparin facilitated complex formation between a-thrombin and antithrombin III, it had little effect on the interaction between p-thrombin and antithrombin III. ... 

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