332 ALBERT DORFMAN AND SARA SCHILLER 



made similar observations. The difference between the physical-chemical 

 properties of keratosulphate and chondroitinsulphuric acids-A and -C 

 may be responsible for changes in the physical properties of cartilage and 

 nucleus pulposus observed with increased age. These facts have obvious 

 implications with respect to the pathogenesis of collapse of intervertebral 

 discs. 



Heparin monosulphuric acid was isolated by Jorpes and Gardell [31] 

 in 1948 from a commercial preparation of heparin. Like heparin, it was 

 found to contain glucosamine and to demonstrate a positive optical rotation. 

 In contrast to heparin, N-acetyl groups and approximately one mole of 

 sulphate per disaccharide were found. Subsequently, Linker et al. [32] 

 isolated a similar compound from the liver of a patient with amyloidosis 

 and from aorta. They named the substance heparitin sulphate. Large 

 amounts of a similar compound have been isolated from the urine and 

 tissues of patients with the Hurler syndrome by Brown [33], Dorfman, 

 and Lorincz [21], and Meyer et al. [34]. Hen oviducts [35] and a mast cell 

 tumour [36] have also been shown to contain a similar substance. 



Heparin monosulphuric acid is characterized by a high colour yield in 

 the Dische carbazole reaction for uronic acid, a positive optical rotation, 

 less than one mole of acetyl per disaccharide unit, and variable sulphate 

 content. In a recent study, Cifonelli and Dorfman [37] have shown that a 

 number of compounds can be separated from a crude preparation, obtained 

 as a by-product of heparin by the Upjohn Company. These materials all 

 exhibited a positive optical rotation and contained both N- and 0-sulphate 

 as well as N-acetyl. The total of N-acetyl and N-sulphate was approxi- 

 mately I. The N-acetyl content of most fractions approximated 0-7 

 mole per disaccharide unit. Preparations which manifested high N-acetyl 

 values contained virtually no N-sulphate. Preliminary studies of the 

 structure of these compounds suggest that they are not linked through the 

 3 position of the hexosamine as are the chondroitin sulphates and hyalu- 

 ronic acid, but are probably linked through the 6 position of hexosamine 

 [38]. These substances have little, if any, antithrombic or anticoagulant 

 properties. Their origin and metabolic importance have not been clarified 

 but chemical properties suggest a relationship to heparin. They may 

 represent intermediates in the biosynthesis of heparin. 



Heparin has been studied intensively from a biological point of view 

 but its chemistry is yet poorly understood. It contains more than 2 sulphate 

 groups per disaccharide unit and demonstrates a positive optical rotation. 

 Unlike other acid mucopolysaccharides it has an N-sulphate group but no 

 N-acetyl group. In addition, one to two sulphate groups per disaccharide 

 repeating unit are present in other parts of the molecule. 



The striking anticoagulant properties of heparin are well known. 

 However, its role in the homeostasis of blood coagulation is not clear. 



