Hydrolases in Developing Rat Brain

It is not yet clear whether lysosomal enzymes act only in degenerative processes, in response to noxious stimuli, or whether they act in the normal degradative processes of turnover. In support of the latter belief is the observation that specific lysosomal enzymes are absent (or highly deficient) in certain genetic lesions characterized by accumulation of the intermediates on which they act 6,7,9,21,23. Another type of evidence comes from comparison of turnover rates and specific activities of lysosomal enzymes: hydrolases occurring in a tissue at relatively high levels should correlate with substances that undergo relatively high turnover. Still further evidence for normal functioning might come from comparisons of changes with age in level of substrate and hydrolase. The last two approaches have been used in this and a preceding study 4. It was shown that there is appreciable parallelism between the concentrations ofgalactosylceramide and the galactosidase which acts on it in the brains of developing rat~. Ceramide hydrolase, on the other hand, follows a pattern more like that of ganglioside concentration. Ceramide appears to be an intermediate in the breakdown of both galactosylceramide and ganglioside, as well as sphingomyelin 2,r~,14. Since ganglioside has a somewhat higher turnover rate than galactosylceramide 18,~2, one might expect to find ceramide hydrolase following the developmental pattern of the former lipid. Glucosylceramide and lactosylceramide ('lactoside') appear to be additional intermediates in the breakdown of ganglioside, so their hydrolases were examined in this study in an effort to extend the parallelism. By way of comparison, sphingomyelinase (a cholinephosphohydrolase) and galactosylphenol hydrolase were also determined. The latter is probably not a single enzyme but rather a conglomerate of/¢galactosidases exhibiting activity toward phenolic galactosides. Evidence is presented