The Protein Activator Specific for the Enzymic Hydrolysis of GM2 Ganglioside in Normal Human Brain and Brains of Three Types of GM2 Gangliosidosis

Abstract: In order to understand the etiology of Type AB GM2 gangliosidosis, we have purified and characterized the activator protein (GM2 activator) specific for the enzymic hydrolysis of GM₂ ganglioside from normal human brain. The purified activator from human brain moved as one major protein band in various electrophoretic systems. We have also prepared the antiserum against this activator. The levels and the nature of GM₂ activator and β-hexosaminidase A were examined in the brains of five cases of GM₂. gangliosidosis—one Type B, two Type O, and two Type AB. We found that the levels of GM₂ activator in both Type B and Type O cases were markedly elevated, and that the two Type AB cases were the results of different causes. One case had a defective β hexosaminidase A and an elevated level of GM₂ activator. Although this defective β-hexosaminidase A could hydrolyze synthetic substrates, it was inactive in the cleavage of natural glycosphingolipids in the presence of the GM₂ activator. It could, however, hydrolyze asialo-GM₂ and GbOse₄Cer in the presence of sodium taurodeoxycholate. The other case had normal β-hexosaminidase A, but had a very low level of GM₂ activator when analyzed by in vitro assay, suggesting the deficiency of this activator. By immunoelectrophoresis, this case was found to be completely devoid of the protein that cross-reacts with the antiserum against the GM₂ activator.