Zur Kenntnis der Gehirnganglioside

Abstract

Studies are reported on the constitutional determination of 4 further hexosamine-containing ganglioside (C1, C2, C3 and C4) from human brain. Like the previously described gariglioside B1, they are converted into ganglioside A2 by the action of neuraminidase, whereby C1 gives one molecule of N-acetyl-neuraminic acid, C2 and C3 each give 2 molecules, and C4 yields 3 molecules. C1 and C3 are the 2 main components of the ganglioside fraction C. The structural formulae proposed for them are based on the fact that stearyl-sphin-gosyl-glucoside, stearyl-sphingosyl-lactoside and [beta] -D-galactosido-(1[forward arrow]3)-(N-acetyl)-D-galactosamine are the main cleavage products from the mild acid hydrolysis; 2, 3, 6-tri-O-methyl-glucose, 2, 6-di-O-methyl-galactose, 2, 3, 4, 6-tetra-O-methyl-galactose and 4, 6-di-O-methyl-galactosamine are produced from the permethylated ganglioside C1; C3 gave the same methylated sugars after mild acid hydrolysis, except that 2, 3, 4, 6-tetra-O-methyl-galactose was replaced by 2, 4, 6-tri-O-methyl-galactose. Further information about the structure of these substances was obtained from a detailed study of their behaviour towards NaIO4- In both gangliosides, one of the 2 or 3 N-acetyl-neuraminic acid residues is not available to the action of NaIO4. After mild treatment with NaIO4, followed by reduction with NaBH4 and treatment with neuraminidase, ganglioside C1 is converted into ganglioside A1. In the same way, ganglioside C3 is converted into ganglioside A2. The NaIO4-insensitive N-acetyl-neuraminic acid residue in both gangliosides must therefore be at position 3 of the middle galactose residue. In both gangliosides, this N-acetyl-neuraminic acid residue is substituted at position 8 by a further molecule of N-acetyl neuraminic acid. Consequently, a dimeric form of N-acetyl-neuraminic acid can be prepared in small amounts from the especially mild acid hydrolysis of ganglioside C1. The results from the action of NaIO4 on the gangliosides under different conditions also agree with the proposed formulae. Ganglioside C2 is an isomer of ganglioside C3 and differs from the latter in that 1 of the % galactose residues of the ganglioside molecule is available to attack by perio-date. Ganglioside C4 differs from C3, however, in that yet a 4th N-acetyl-neuraminic acid residue is present in the ganglioside molecule. According to the obtained findings, it should be present at position 8 on 1 of the 2 terminal N-acetyl-neuraminic acid residues of ganglioside C3.