Open AccessSphingolipid biosynthesis in cultured neurons
Author(s) -
MANDON Elisabet C.,
ECHTEN Gerhild,
BIRK Rolf,
SCHMIDT Richard R.,
SANDHOFF Konrad
Publication year - 1991
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1111/j.1432-1033.1991.tb16065.x
Subject(s) - sphingolipid , sphingosine , biosynthesis , biochemistry , ceramide synthase , serine , ceramide , enzyme , chemistry , sphingomyelin , phospholipid , atp synthase , lysophospholipase , stereochemistry , biology , lipid signaling , membrane , phospholipase , apoptosis , receptor
Addition of exogenous sphingosine homologues (D‐ erythro configuration) with different alkyl chain lengths (12 and 18 carbon atoms) to the medium of primary cultured cerebellar cells resulted in a decrease of serine palmitoyltransferase activity in a time‐ and concentration‐dependent manner. This enzyme catalyzes the first committed step in sphingolipid biosynthesis. Half‐maximal reduction of enzyme activity occurred after a 4‐h treatment with 25 μM sphingoid bases. Maximal decrease (approx. 80%) was obtained after treating the cells for 4–8 h with 50 μM long‐chain bases. When a biosynthetically inert sphingoid, azidosphingosine (10–50 μM), was fed to the cells, decrease of 3‐ketosphinganine formation was much slower, reaching its maximum (approx. 80%) after 24 h. In contrast to D‐ erythro ‐sphingosine, L‐ threo ‐C 18 ‐sphingosine did not yield any decrease of serine palmitoyltransferase activity when added to the cells under identical experimental conditions. Decrease of serine palmitoyltransferase activity was fully reversible after removal of the long‐chain bases from the culture medium. Activities of other enzymes of lipid metabolism, ceramide synthase, long‐chain acyl‐CoA synthase and choline phosphotransferase, were not affected by the addition of sphingoid bases, indicating that the down regulation of serine palmitoyltransferase is quite specific.