MUCOPOLYSACCHARIDES OF CONNECTIVE TISSUE 333 



Heparin has not been isolated from blood but there is no doubt that it is 

 present in mast cells. The possible physiological role of heparin assumed 

 increased importance with the discovery that injection of heparin induced 

 the release of a lipase responsible for " clearing" of blood [39]. The relation 

 of these observations to fat metabolism and arteriosclerosis is obvious. 



The foregoing discussion reviews briefly the status of knowledge 

 regarding chemical structure and biological function of the acid muco- 

 polysaccharides of connective tissues. Alterations in tissue functions may 

 be a reflection of changes in metabolism of these substances. Clarification 

 of the metabolism of acid mucopolysaccharides required first a delineation 

 of the pathways of biosynthesis. These have been reviewed extensively 

 elsewhere [40]. 



Briefly, Alarkovitz et a/. [41] have shown that the acid mucopoly- 

 saccharide, hyaluronic acid, is formed from uridine diphosphoglucuronic 

 acid and uridine diphospho-N-acetylglucosamine by an enzyme isolated 

 from a strain of Group A streptococci. Although attempts to solubilize 

 this enzyme have not been successful, it has been possible to show that the 

 enzyme resides on the protoplast membrane [41]. Of interest, is the recent 

 report by Smith et al. [43] that Type III pneumococcal capsular poly- 

 saccharide is synthesized from uridinediphosphoglucuronic acid and 

 uridinediphosphoglucose. 



Early studies on the metabolism of the acid mucopolysaccharides were 

 concerned with rates of turnover in mammalian connective tissue. Skin 

 was used as a source of connective tissue since it contains acid mucopoly- 

 saccharides in sufficient quantity for isolation and degradation [20]. The 

 rate of turnover of hyaluronic acid and a chondroitin sulphuric acid fraction 

 was determined in both rats and rabbits by utilizing [^^C]-glucose and 

 -acetate as well as ^'SO^, as precursors [44]. Glucose is a precursor of the 

 uronic acid and hexosamine moieties of the mucopolysaccharides ; acetate 

 is a precursor of the acetyl groups; and ^^SOj" is incorporated as ester 

 sulphate. These experiments showed that hyaluronic acid, with a half-life 

 of approximately 2 • 5 days, w^as metabolized at a rate comparable to other 

 metabolically active substances [45]. Chondroitin sulphuric acid was 

 metabolized more slowly. The rate of turnover was found to be similar 

 when measured with acetate, glucose, or sulphate, indicating complete 

 turnover of the entire molecule. Sulphate has been used by many investiga- 

 tors to label acid polysaccharides in diverse tissues. 



Having determined these parameters of normal metabolism it was 

 possible to utilize similar techniques for a study of the efl^ects of hormones. 

 Cortisone and hydrocortisone were found to decrease the rate of turnover 

 of both the sulphated and non-sulphated mucopolysaccharides of skin [46]. 

 This inhibition is time-dependent. Although the mechanism of action of 

 the adrenal hormones is unknown, this metabolic effect may be responsible 



