title: Inhibition of sterol but not fatty acid synthesis by valproate in developing rat brain in vivo.
abstract: 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.
authors: Nuffield Department of Clinical Medicine, Radcliffe Infirmary, Oxford, U.K.
authors: J P
authors: JP
authors: Bolaños
authors: J M
authors: JM
authors: Medina
authors: D H
authors: DH
authors: Williamson
mesh_terms: 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*
chemical_list: D005227:Fatty Acids; D013261:Sterols; D014316:Tritium; D014635:Valproic Acid; D008798:Mevalonic Acid