title: Effect of modification of sialic acid on enzymic hydrolysis of gangliosides GM1 and GM2.
abstract: In order to understand the mechanism of action of the activator proteins for the enzymic hydrolysis of GM1 (GM1-activator; Li, S.-C. and Li, Y.-T. (1976) J. Biol. Chem. 251, 1159-1163; for ganglioside designations, see Svennerholm, L. (1963) J. Neurochem. 10, 613) and GM2 (GM2-activator; Li, S.-C., Hirabayashi, Y., and Li, Y.-T. (1981) J. Biol. Chem. 256, 6234-6240), we have studied the effect of chemical modifications of GM1 and GM2 on their susceptibility to the activator-assisted enzymic hydrolysis. Chemically modified GM1 and GM2 were prepared by methyl esterification (Me-GM1 or Me-GM2) and reduction (HO-GM1 or HO-GM2) of the -COO- group of the sialic acid. Me-GM1 and HO-GM1 could be hydrolyzed by human hepatic beta-galactosidase in the presence of GM1-activator at rates comparable to that of the native GM1. However, in contrast to native GM2, Me-GM2 and HO-GM2 were resistant to the hydrolysis by human hepatic beta-hexosaminidase A in the presence of GM2-activator. When GM2-activator was replaced by sodium taurodeoxycholate, the native GM2 and both modified GM2 could be hydrolyzed by beta-hexosaminidase A. These results suggest that the carboxyl function of sialic acid in GM1 is not vital for beta-galactosidase or GM1-activator to carry out the cleavage of the terminal Gal. In the case of GM2 hydrolysis, the carboxyl function of sialic acid is involved in the interaction with GM2-activator. Our results also indicate that the mode of action of GM1-activator is different from that of GM2-activator and that the action of GM2-activator is different from that of sodium taurodeoxycholate.
mesh_terms: D001921:Brain / Q000378:metabolism*; D005677:G(M1) Ganglioside / Q000378:metabolism*; D005678:G(M2) Ganglioside / Q000378:metabolism*; D005696:Galactosidases / Q000378:metabolism*; D005732:Gangliosides / Q000378:metabolism*; D006596:Hexosaminidases / Q000378:metabolism*; D006801:Humans; D006868:Hydrolysis; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D012794:Sialic Acids / Q000032:analysis*; D013661:Tay-Sachs Disease / Q000378:metabolism*; D001616:beta-Galactosidase / Q000378:metabolism*; D001619:beta-N-Acetylhexosaminidases
chemical_list: D005732:Gangliosides; D012794:Sialic Acids; D005678:G(M2) Ganglioside; D005677:G(M1) Ganglioside; D005696:Galactosidases; D006596:Hexosaminidases; D001616:beta-Galactosidase; D001619:beta-N-Acetylhexosaminidases