330 ALBERT DORFMAN AND SARA SCHILLER 



role of chondroitin sulphuric acids in calcification has been considered 

 but no mechanism has been clarified [lo]. Chondroitin sulphuric acid-A 

 diflFers from chondroitin sulphuric acid-C only in that the sulphate group 

 is esterified at carbon 4 of the galactosamine rather than at position 6. 

 The relationship of the sulphate position to the calcification process 

 merits further consideration. It is of interest to note that chondroitin 

 sulphuric acid-C predominates in elasmobranch cartilage which is not 

 converted into bone [11]. The interrelationships of chondroitin sulphuric 

 acids and collagen are not entirely clarified. Jackson [12] found that 

 treatment of tendon with hyaluronidase increased the solubility of collagen. 

 Chondroitin sulphuric acid-B is distinguished from chondroitin 

 sulphuric acids-A and -C by the presence of L-iduronic acid instead of 

 D-glucuronic acid [13, 14]. The sulphate group occupies the same position 

 as is characteristic of chondroitin sulphuric acid-A [2]. Figure 2 shows the 



H 



y^^ \h 



OH H 



OH OH\| 1/ OH 



H OH 



D-glucuronic acid L-iduronic acid 



Fig. 2. The structures of D-glucuronic acid and L-iduronic acid. 



structure of L-iduronic acid compared with that of D-glucuronic acid. The 

 two uronic acids are epimers difiFering only with respect to the stereiso- 

 merism at C-5. L-idose has not been identified in natural materials, but 

 L-iditol has been found in mountain ash berry by de Bertrand [15] in 1905. 

 Chondroitin sulphuric acid-B (/3-heparin) was isolated by Marbet and 

 Winterstein [16] from a commercial preparation of heparin and because 

 of its anticoagulant properties was believed to be an isomer of heparin. 

 It was found to be more potent as an antithrombic substance than as a 

 whole blood anticoagulant. Grossman and Dorfman [17] found that the 

 antithrombic activity of chondroitin sulphuric acid-B varied with the 

 concentration of thrombin. At low thrombin concentrations it is more 

 active than heparin, but at high thrombin concentrations it is inactive. 

 Like heparin, chondroitin sulphuric acid-B requires for activity a plasma 

 cofactor, the natural plasma antithrombin. In the absence of plasma it is 

 completely inactive. On whole blood the anticoagulant activity is only 5% 

 that of heparin. The physiological importance of the antithrombic activity 

 of chondroitin sulphuric acid-B is obscure. The relatively high concentra- 

 tion in certain tissues may permit a significant homeostatic role in the 

 regulation of fibrinogen-fibrin conversion within tissues. 



