Coudé F X, Grimber G, Pelet A, Benoit Y
Biochem Biophys Res Commun. 1983 Sep 15;115(2):730-6. doi: 10.1016/s0006-291x(83)80205-8.
Valproate at 0.1 to 5 mM strongly inhibited oxidation of 1-(14C)-palmitate in isolated rat hepatocytes. Valproate at the same concentrations markedly decreased ketogenesis from 1 mM oleate. Valproate in a dose up to 5 mM did not significantly affect cellular concentration of ATP but lowered beta-hydroxybutyrate/acetoacetate and lactate/pyruvate ratios which paralleled its effect on ketogenesis. Moreover concomitant acetyl-CoA levels were drastically decreased by valproate. From this it may be concluded that inhibition of fatty acid oxidation by valproate results in reduced production of two carbons units and a drop of NADH/NAD+ ratio in rat hepatocyte. This suggests that valproate seriously interferes with beta-oxidation of physiological long-chain fatty acids.
0.1至5毫摩尔的丙戊酸盐能强烈抑制分离出的大鼠肝细胞中1-(14C)-棕榈酸盐的氧化。相同浓度的丙戊酸盐能显著降低1毫摩尔油酸生成酮体的量。高达5毫摩尔剂量的丙戊酸盐对细胞内三磷酸腺苷（ATP）的浓度没有显著影响，但降低了β-羟基丁酸/乙酰乙酸和乳酸/丙酮酸的比值，这与其对酮体生成的影响相平行。此外，丙戊酸盐能使乙酰辅酶A的水平急剧下降。由此可以得出结论，丙戊酸盐对脂肪酸氧化的抑制作用导致大鼠肝细胞中两个碳单位的生成减少以及烟酰胺腺嘌呤二核苷酸（NADH）/烟酰胺腺嘌呤二核苷酸（NAD+）比值下降。这表明丙戊酸盐严重干扰了生理长链脂肪酸的β-氧化。
