On the chemistry of heparin

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Abstract
The protein-free polysaccharide carrying heparin activity is quite different if prepd. from different organs. The organic skeleton seems to be the same, namely, an acetylated amino-sugar combined with a hexuronic acid. The preps, differ in S content and anticoagulant activity, the liver heparins being the most active. The preps, are all inhomogeneous. From all of them, fractions with a higher S content can be isolated either as Ba or as brucine salts. Do these fractions with varying S content really occur in the living animal or are they secondary degradation products arising during the process of prep.? The former alternative is the most probable, because the heparin with the highest S content is very resistant. It is stable enough to resist both autolysis of the organs and tryptic digestion, and also alkaline extraction with subsequent acidification; it will therefore hardly give rise to any considerable amt. of fractions with lower S content. These polysaccharide fractions with lower S content also possess a certain anticoagulant activity. The biological activity is probably not due to admixture with the more active mucoitin trisulphuric acid, because the fractions are obtained from the mother liquors after removal of the less soluble brucine of Ba salts of the trisulphuric acid. The possibility that the more soluble salts influence the solubility in water of the less soluble salts of the trisulphuric acid is not excluded. It seems as if all these different fractions carry an anticoagulant activity of their own, rapidly decreasing with decreasing S content. The recent findings of Jaques, that there is a sp. specificity, also add further evidence on this point. Heparin from dog liver is 2.5 times more active than ox liver heparin with the same S content. Taking into account also the fact that heparins with about the same S content originating from different organs show different anticoagulating effects, the liver heparins being the strongest, heparin cannot be considered a homogeneous compound in the same sense as the other crystalline hormones, such as insulin. In order to explain the exceptionally high biological activity of dog heparin, an attempt was made at isolating a tetrasulphuric acid as brucine salt from dog liver heparin. No fraction with a higher S content than that of the trisulphuric acid could, however, be obtained. While the fact still remains, that the exceptionally strong electric charge and the molecular configuration are the most outstanding properties of the heparin polysaccharide, there is very little known about the ultimate underlying principle causing the anticoagulating activity.