Structure-function relationships of heparin species.
We have fractionated porcine heparin species of low molecular weight, with an average specific anticoagulant activity of 96 units/mg by affinity chromotography. Highly active and relatively inactive preparations of similar size were obtained with specific anticoagulant activities of 360 and 4 units/mg, respectively. The highly active heparin fraction possesses 1.1 additional residues of glucuronic acid and 1.5 fewer residues of N-sulfated glucosamine per molecule compared to the relatively inactive species. This decrease in N-sulfated glucosamine appears to be secondary to a corresponding increase in N-acetylated glucosamine. This form also contains a tetrasaccharide sequence with a N-sulfated glucosamine at its reducing end as well as equivalent amounts of glucuronic acid and iduronic acid. Furthermore, the internal glucosamine residue of this sequence appears to be N-acetylated. Sufficient amounts of this tetrasaccharide sequence are present within the highly active preparation such that each molecule may be endowed with this structure. The relatively inactive product contains a significantly decreased quantity of this tetrasaccharide sequence such that only [unk]20% of these molecules may possess this structure. The mean distance between nonsulfated uronic acid residues of the highly active species is smaller than that separating similar residues of the relatively inactive product. In addition, a larger number of the nonsulfated uronic acid residues of the highly active material appears either to be present in a restricted region of the molecule separated only by glucosamine residues or to be located at penultimate positions within the polysaccharide chain.
D000818:Animals; D000991:Antithrombins / Q000378:metabolism; D005944:Glucosamine / Q000032:analysis; D005965:Glucuronates / Q000032:analysis; D006493:Heparin / Q000032:analysis* / Q000302:isolation & purification / Q000494:pharmacology; D006801:Humans; D008970:Molecular Weight; D013329:Structure-Activity Relationship; D013431:Sulfates / Q000032:analysis; D013552:Swine; D014574:Uronic Acids / Q000032:analysis
D000991:Antithrombins; D005965:Glucuronates; D013431:Sulfates; D014574:Uronic Acids; D006493:Heparin; D005944:Glucosamine