Inhibition of sterol but not fatty acid synthesis by valproate in developing rat brain in vivo. |
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Authors: | J P Bola?os J M Medina and D H Williamson |
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Institution: | Nuffield Department of Clinical Medicine, Radcliffe Infirmary, Oxford, U.K. |
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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. |
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