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Inhibition of Sphingolipid Synthesis by Cycloserine In Vitro and In Vivo
Author(s) -
Sundaram K. Soma,
Lev Meir
Publication year - 1984
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1984.tb02716.x
Subject(s) - cycloserine , in vivo , microsome , enzyme , sphingolipid , in vitro , biochemistry , chemistry , ganglioside , biology , antibiotics , microbiology and biotechnology
d ‐ and l ‐cycloserine were shown to be irreversible inhibitors of the first enzyme of the sphingolipid pathway, 3‐ketodihydrosphingosine synthetase, in a study using bacterial and brain microsomal enzymes, l‐Cycloserine was shown to be 100 times more inhibitory than the d‐isomer for the brain microsomal enzyme in vitro. In vivo , l ‐cycloserine caused a 70% inhibition of brain microsomal enzyme. Following one injection, enzyme activity recovered 80% of normal after 16 hours. Daily dosages of l ‐cycloserine on a regimen of intraper‐itoneal injection for 7 days caused a significant reduction in total brain ganglioside and cerebroside plus sulfatide levels.