Effect of modification of sialic acid on enzymic hydrolysis of gangliosides GM1 and GM2.
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.
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
D005732:Gangliosides; D012794:Sialic Acids; D005678:G(M2) Ganglioside; D005677:G(M1) Ganglioside; D005696:Galactosidases; D006596:Hexosaminidases; D001616:beta-Galactosidase; D001619:beta-N-Acetylhexosaminidases