The protein activator specific for the enzymic hydrolysis of GM2 ganglioside in normal human brain and brains of three types of GM2 gangliosidosis.

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 GM 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 beta-hexosaminidase A were examined in the brains of five cases of GM2 gangliosidosis-one Type B, two 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 beta-hexosaminidase A and an elevated level of GM2 activator. Although this defective beta-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 beta-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.