Inhibition of sterol but not fatty acid synthesis by valproate in developing rat brain in vivo.
The effect of administration of valproate on lipogenesis in the developing rat brain in vivo was studied. Valproate inhibited by 21-38% the rate of 3H2O incorporation into brain sterols, without significantly affecting fatty acid synthesis. Similarly, R-[2-14C]mevalonate incorporation into sterols was inhibited by 33-54%; the low rate of fatty acid synthesis under these conditions was not affected by valproate. Plasma ketone bodies decreased after treatment with valproate. Valproate inhibited (about 50%) both sterol and fatty acid synthesis in livers of weanling rats. It is concluded that valproate can specifically inhibit sterol synthesis in the brain during development, in part at a stage after mevalonate formation, and also by decreased exogenous precursor supply.
Bolaños
J P
JP
Nuffield Department of Clinical Medicine, Radcliffe Infirmary, Oxford, U.K.
Medina
J M
JM
Williamson
D H
DH
D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism; D005227:Fatty Acids / Q000096:biosynthesis*; D007700:Kinetics; D008798:Mevalonic Acid / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013261:Sterols / Q000096:biosynthesis*; D014316:Tritium; D014635:Valproic Acid / Q000494:pharmacology*
D005227:Fatty Acids; D013261:Sterols; D014316:Tritium; D014635:Valproic Acid; D008798:Mevalonic Acid