Correlation between structure, fat-clearing and anticoagulant properties of heparins and heparan sulphates.
Heparins and heparan sulphates from different organs, of high purity by accepted criteria, were characterized by chemical and physical (including electrophoretic and 13C-NMR spectroscopic) methods. The fat-clearing activity of these preparations was shown to be correlated with their content of the trisulphated disaccharide units I2S-ANS,6S (L-iduronic acid 2-O-sulphate-N-sulphated D-glucosamino 6-O sulphate). Species with low anti-lipemic activity contained significant proportions (greater than or equal to 30%) of nonsulphated uronic acids (especially D-glucuronic acid), and of D-glucosamino residues undersulphated at C-6, these latter residues being partially N-acetylated. Heparins from beef lung and sheep mucosa, predominantly consisting of trisulphated disaccharide units, displayed consistently higher antilipemic activity than the more heterogeneous pig mucosal heparins. The anticoagulant activity (as determined by the U.S.P., APTT and anti-Xa tests) was not a simple function of the measured physicochemical parameters. Trends were confirmed for pig mucosal heparins being more anticoagulant than beef lung preparations, and low molecular weight (usually undersulphated) species being more active in the anti-Xa test than in the U.S.P. and APTT tests.
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D000925:Anticoagulants; D002417:Cattle; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004586:Electrophoresis; D006025:Glycosaminoglycans / Q000494:pharmacology*; D006493:Heparin / Q000494:pharmacology*; D006497:Heparan Sulfate / Q000494:pharmacology*; D000960:Hypolipidemic Agents; D066298:In Vitro Techniques; D008071:Lipoprotein Lipase / Q000378:metabolism; D008970:Molecular Weight; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D013552:Swine
D000596:Amino Acids; D000925:Anticoagulants; D006025:Glycosaminoglycans; D006493:Heparin; D006497:Heparan Sulfate; D000960:Hypolipidemic Agents; D008071:Lipoprotein Lipase