Reaction mechanism hyaluronidases

While all hyaluronidases can bring about the depolymerization of hyaluronic acid, the individual enzymes differ considerably in specificity, reaction mechanism, and the products of the catalyzed reaction (Meyer el al., 1960 Gibian, 1966). Apart from an enzyme from leech (an endo- glucuronidase) (Meyer el al., 1960), all other known hyaluronidases act upon the ondohexosarainide linkages. 

The intense staining for HA in psoriatic lesions may in part be due to partially degraded HA, and may be the mechanism for the marked capillary proliferation and inflammation that characterizes these lesions.53,57-59 Attempts to stimulate HA deposition for purposes of promoting skin hydration must use caution that the HA deposited remain high molecular weight, by preventing free radical-catalyzed chain breaks and by carefully restricting the catabolic reactions of the hyaluronidases. 

Increased HA levels in the bloodstream decrease immune competence.153 Various mechanisms have been invoked. An HA coating around circulating lymphocytes may prevent ligand access to lymphocyte surface receptors.95 96 154 155 The increased HA may represent one of the mechanisms for the immunosuppression in the fetus. The reappearance of high levels of HA in old age may be one of the mechanisms of the deterioration of the immune system in the elderly. The increasing levels of HA with aging may be a reflection of the deterioration of hydrolytic reactions, including the hyaluronidases that maintain the steady state of HA. This is a far more likely mechanism than an increase in HA synthase activity. 

This type of enzyme is commonly obtained from bacterial sources like pneumococci, staphylococci, streptococci, Clostridia [29], Flavobacterium, and Proteus vulgaris [30], and has been demonstrated in Treponema pallidum [31]. Bacterial hyaluronidases degrade hyaluronan to a disaccharide containing a A-4,5-unsaturated uronic acid by eliminating 1 mole of water from the uronic acid portion of the repeating unit of hyaluronan [29]. The full mechanism of this type of reaction has been elucidated by Ludowieg et al. [32],... 

In vitro, the reaction of ascorbate with hyaluronic acid and with chondroitin sulfate has been reported to yield breakdown products of somewhat lower viscosity than the original preparations (303), Ascorbic acid also inhibits hyaluronidase in vitro under conditions that preclude the possibility of PHI production, but it has been shown to have a much greater effect in vivo, clearly indicating the existence of some intermediate mechanism (267). 

---