Brain sialidase substrate specificity

C. Oehler, J. Kopitz, and M. Cantz, Substrate specificity and inhibitor studies of a membrane-bound ganglioside sialidase isolated from human brain tissue, J. Biol. Chem., 383 (2002) 1735-1742. 

Sialidase activities in light and heavy lysosomal fractions have been characterized in rat mammary gland (Tulsiani and Carubelli, 1971), human liver (Meyer et al., 1981), and mouse brain (Fiorilli et al., 1991). The heavy lysosomal fraction shows higher specific enzyme activity than the light fraction, but there is no difference in pH optimum, value, or substrate specificity between the two fractions. In mouse brain, the sialidase activities in the heavy and light lysosomal fractions exhibit different developmental profiles, suggesting that the expression of these activities may be regulated independently (Fiorilli et al.y 1991). 

Other compounds tested for their ability to inhibit or activate sialidase include iodoacetamide (10 m). AT-ethylmaleimide (10 m) and Mersalyl (10 m). On partially purified sialidase from pig kidney, these had no effect (Tuppy and Palese, 1968) a-chymotrypsin with sialidase from bovine brain caused an increase in activity (Gielen and Harprecht, 1969) EDTA, p-hydroxymercuribenzoate (formerly was believed to be p-chloromercuribenzoate), tested on sialidase in rat liver and kidney, had no effect (Mahadevan et al., 1967) the bacterial inhibitors 2-deoxy-2,3-dehydroneuraminic acid and p-nitrophenyloxamic acid tested on purified sialidase from rat heart muscle had no effect (Tallman and Brady, 1973) while l-(4-methoxyphenoxymethyl)-3,4-dehydroisoquino-line and p-hydroxymercuribenzoate were inhibitory with ganglioside Goia substrate. The effect of specific inhibitors on purified sialidase may give useful information about the active site, an unknown entity at this time. 

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