The galactosyl moiety of brain cerebrosides

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Thirteen years ago I found that galactosyl ceramide undergoes metabolic conversion in the brain of young ratsa). Month-old rats were injected with 14C-galactose, rats were sacrificed at various intervals, and the brain lipids were fractionated according to the following scheme (fig. 1). The radioactivity in the galactose of each lipid group is shown in fig. 2, which plots total activity against time. The top curve, from cerebrosides, shows a slow but distinct conversion of brain cerebroside. Judging by the somewhat slower rate of rise in sulfatide activity (bottom curve), this conversion could - in part, at least - be due to conversion of cerebroside to sulfatide. Confirmation of this guess came from the work of Bachhawat and McKhann some years later z, 3). (The middle curve, for gangliosides, shows this group of lipids has a higher turnover rate than cerebrosides.) There was some reason to believe that another portion of the metabolic conversion of cerebrosides involved hydrolysis of the galactosidic linkage. Fujino 4) and Thannhauser and Reichel ~) had reported rather incomplete evidence for the presence in brain of a cerebroside galactosidase, and it was also known that cerebrosides can disappear in demyelinative processes. Accordingly, we made some radioactive cerebroside and looked for the hydrolysis. The preparation of the labeled lipid was based on a procedure of Carter and Fujino 6) for the formation of psychosine sulfate (fig. 3). The first reaction is formulated in an unusual way in order to explain something we found a few years later: when a mixture of cerebrosides is used, containing both hydroxy and nonhydroxy fatty acids, one obtains a great deal of unhydrolyzed cerebroside of the latter type. Carter and Koob simultaneously made a similar observation. We have not made a serious study of the reaction, but it looks as though only the hydroxy fatty acid amide bond is attacked by the barium ions, and I suggest the effect involves formation of a barium chelate ofhydroxy fatty acids, shown in the top equation. The last step in the synthesis is an adaptation of the procedure of Shapiro