Hyaluronidases structure

Enzymes DegradingMacromolecules. Enzymes that degrade macromolecules such as membrane polysaccharides, structural and functional proteins, or nucleic acids, have all shown oncolytic activity. Treatment strategies include the treatment of inoperable tumors with pepsin (1) antitumor activity of carboxypeptidase (44) cytotoxicity of ribonudease (45—47) oncolytic activity of neuraminidase (48—52) therapy with neuraminidase of patients with acute myeloid leukemia (53) antitumor activity of proteases (54) and hyaluronidase treatment in the management of human solid tumors (55). 

Flavonoids are well known as inhibitors of hyaluronidase. Li 1950 Rodney et al, reported the effect of several flavonoids on hyaluronidase using in vitro and in vivo methods [79], Knppusamy et al. investigated the structure-activity relationship of die flavonoids as inhibitors of testicular hyaluronidase [80] and hyaluronidase from snake, scorpion, and bee venom [81]. They showed that flavones. flavanols. and chalcones possess the general ability to inhibit hyaluronidase Kinetic investigations showed that these compounds acted as competitive inhibitors [80]. Several hyaluronidase inhibitors were shown to be able to delay the action of snake venom when injected into mice [8ll One caimnt rule out the possible interaction of the flavonoids with other components of the venom, as the inhibitory effects of flavonoids are not specific to hyaluronidase... 

L. Fraosson and L Roddn. Structure of dermatan sulphate I. Degradation by testicular hyaluronidase. J. Bid Chem. 242 4161 (1967). 

Tissues that contain high molecular weight HA are unusually resistant to invasion and penetration.49 Blood vessels are unable to penetrate joint synovium, cartilage, and the vitreous of the eye. It is also unusual for tumor metastases to develop in these structures. It may be the large size of the HA polymer that also protects such structures from invasion by parasites. The mechanism by which such high molecular weight structures resist hyaluronidase degradation, and avoid the rapid HA turnover characteristic of the rest of the body is not known. Potent hyaluronidase inhibitors may be involved, a class of molecules about which little is known. 

Levels of HA that cells deposit must respond to various physiological states including growth phase,239 confluence, inversely related to cell density in both fibroblasts,240 and keratinocytes,241 mitosis and cell detachment from the substratum,242 calcium concentrations,149,243 anoxia and lactate,244 viral transformation,245 and serum stimulation.91,246 Preliminary immunolocalization data indicate that some of the HAS and hyaluronidases colocalize (A. Spicer et al., pers. commun.). All of this evidence supports, albeit indirect and tentative, the existence of the hyaluronasome structure. 

This mucopolysaccharide, possessing a strueture similar to those of chondroitin 4- and 6-sulfates but with a small content of sulfate, was isolated from bovine cornea (M16). Chondroitin resembles hyaluronic acid in its rate of hydrolysis by testicular and bacterial hyaluronidases, but was differentiated from hyaluronic acid ([a]n —65° to — 78°) by its optical rotation ( [o]d — 21°). Its structural similarity to chondroitin 4- and 6-sulfates was indicated by the fact that chondrosine was released in high yield on controlled, acidic hydrolysis (D3). The isolation of this mucopolysaccharide is of particular interest since it may be a precursor in the biosynthesis of chondroitin 4- and 6-sulfates. 

Heparitin sulfate is composed of D-glucuronic acid, n-glucosamine, acetyl, and sulfate residues in approximately equimolar ratio (J12). The structure of heparitin sulfate still awaits final elucidation, but it may be distinguished from other sulfated mucopolysaccharides by means of its high positive rotation, electrophoretic behavior, and resistance to testicular, bacterial, and leech hyaluronidases. Final identification, however, usually requires its isolation and analysis. 

---