Hyaluronidase lysosomal

Lysosomal hyaluronidase possesses transglycosylation properties using octo-saccharides as a substrate, rather than hexasaccharides like testicular hyaluronidase [14, lti]. 

Alternatively, the calcium stores may be concentrated by lamellar bodies from the intercellular fluids released during terminal differentiation. The lamellar bodies are thought to be modified lysosomes containing hydrolytic enzymes, and a potential source of the hyaluronidase activity. The lamellar bodies fuse with the plasma membranes of the terminally differentiating keratinocytes, increasing the plasma membrane surface area. Lamellar bodies are also associated with proton pumps that enhance acidity. The lamellar bodies also acidify, and their polar lipids become partially converted to neutral lipids, thereby participating in skin barrier function. 

Hyal-1, an acid-active lysosomal enzyme, was the first somatic hyaluronidase to be isolated and characterized.191,192 It is a 57 kDa single polypeptide glycoprotein that also occurs in a processed 45 kDa form, the result of two endoprotease reactions. The resulting two chains are bound by disulfide bonds. This is not a zymogen-active enzyme relationship, since the two isoforms have similar specific activities. Why two forms should occur is unknown. Only the larger form is present in the circulation, while both isoforms occur in urine,193 in tissue extracts, and in cultured cells. Why an acid-active hyaluronidase should occur in plasma is not clear. Some species do not have detectable enzymatic activity in their circulation,194 but an inactive 70 kDa precursor form of the enzyme is present in such sera, detectable by Western blot (L. Shifrin, M. Neeman, and R. Stern, unpubl. data). Hyal-1 is able to utilize HA of any size as substrate, and generates predominantly tetrasaccharides. 

Triggs-Raine, B. et al., Mutations in HYAL1, a member of a tandemly distributed multigene family encoding disparate hyaluronidase activities, cause a newly described lysosomal disorder,mucopolysaccharidosis IX, Proc. Natl Acad. Sci. USA, 96, 6296, 1999. 

Lepperdinger, G., Strobl, B., and Kreil, G., HYAL2, a human gene expressed in many cells, encodes a lysosomal hyaluronidase with a novel type of specificity. J. Biol. Chem., 273, 22466, 1998. 

Kushwah, A., Amma, M.K., and Sareen, K.N., Effect of some anti-inflammatory agents on lysosomal and testicular hyaluronidases, Indian J. Exp. Biol., 16, 222, 1978. 

Natowicz, M.R. and Wang, Y., Plasma hyaluronidase activity in mucolipidoses II and III marked differences from other lysosomal enzymes, Am. J. Med. Genet., 65, 209, 1996. 

Bollet et al. [11] demonstrated the presence of hyaluronidase activity in various mammalian tissues. They showed that this type of hyaluronidase differed from the testicular type concerning pH optimum and pH range of activity. Subsequent studies revealed that the enzyme was present in the lysosomal fraction of the tissues [12]. The liver is an especially rich source [13]. Degradation of hyaluronan leads to the same end products as testicular hyaluronidase [11]. Lysosomal hyaluronidase from rat liver degrades chondroitin-4- and -6-sulfate, but not dermatan sulfate, desulfated dermatan sulfate, heparan sulfate, keratan sulfate, or heparin [14], Lysosomal hyaluronidase has an acid pH optimum and a narrow pH range of activity [14]. This difference in pH profile of activity has commonly been used to differentiate between testicular and lysosomal hyaluronidase. A similar acid-active hyaluronidase is present in human serum [15]. 

Hyaluronidase has an absolute requirement for cations, as dialyzed preparations show no activity toward dialyzed substrates. K+, Na+, Ca2+, Mg2+, and Mn2+ all have stimulating properties toward hyaluronidase. The monovalent cations show the strongest stimulating effects and act over a broader range of concentration than divalent cations [50]. Testicular, serum, and lysosomal hyaluronidase seem to have different sensitivities toward NaCl [54,61]. A noncompetitive mechanism was proposed to explain the activation of hyaluronidase by Na+ [59,62]. 

Hyaluronidases are generally glycoproteins. This has been confirmed for testicular [67], Staphylococcus aureus [68], lysosomal [59], lizard venom [21], and stonefish venom [22] hyaluronidases. The amino acid compositions of testicular [67], Staphylococcus aureus [68], lizard venom [21], and stone-fish venom [22] hyaluronidases have been determined. Of the latter type, the N-terminal sequence has been derived. The hyaluronidase gene of Streptococcus pyogenes bacteriophage H4489A has been expressed in Escherichia coli and the full nucleotide sequence has been derived. This made possible a mapping of the full amino acid sequence of the enzyme [69]. 

B. Fiszer-Szafarz and D. Szafarz. Lysosomal hyaluronidase activity in normal rat liver and in chemically induced hepatomas. Cancer Res. 55 1104 (1973). 

G. N. DeMartino and A. L. Goldberg. A possible explanation of myxededema and hypercholesterolemia in hypothyroidism control of lysosomal hyaluronidase and cholesterol esterase by thyroid hormones. Enzyme 26 1 (1981). 

B. Fiszer-Szafarz. Hyaluronidase polymorphism detected by polyacrylamide gel electrophoresis. Application to hyaluronidases from bacteria, slime molds, bee and snake venoms, bovine testes, rat liver lysosomes and human serum. Anal. Biochem. 143 16 (1984). 

The hyaluronidase (pH optimum 3.9, pi 5.2, mol. wt. 7 x 10 ) obtained from human placenta, by gel filtration and ion-exchange chromatography, is a typical lysosomal enzyme that also depolymerizes chondroitin and chondroitin 4- and 6-sulphates. ... 

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