Chemical Models and Chemotherapy in the Sphingolipidoses
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As I left the previous Sphingolipid Symposium that was held here in 1971, I decided to attempt intervening in glucocerebroside metabolism by synthesizing suitable enzyme inhibitors. It seemed possible to help the victims of Gaucher’s disease, and possibly other sphingolipidoses, by slowing down the synthesis of the sphingolipid that accumulates. When you look at the hydrolase activities reported for the tissues from homozygous individuals suffering from sphingolipidoses, and compare the data with the activities in related, heterozygous individuals, the interesting point emerges: there is really not a great difference in specific activities. Where a sick person might exhibit an activity that is 10% of normal, the apparently healthy relative is getting along fine with an activity that may be 25% of normal. It is apparent that, at least in some organs, many victims of sphingolipidoses are hydrolyzing quite a bit of lipid each day. Their problem seems to be that they are making just a bit too much of the lipid each day and the overload is gradually producing a serious accumulation.
KeywordsDecanoic Acid Hydroxy Acid Brain Microsome Gauche Patient Ceramide Analog
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