Benavides J, Martin A, Ugarte M, Valdivieso F
Biochem Pharmacol. 1982 Apr 15;31(8):1633-6. doi: 10.1016/0006-2952(82)90392-6.
The anticonvulsive drug, valproic acid, inhibits competitively the pyruvate carrier in rat brain and liver mitochondria. Due to this inhibition the oxygen consumption supported by pyruvate oxidation is also affected. In our experimental conditions, pyruvate oxidation is partially inhibited by VPA concentration as low as 0.05 mM. Valproic acid, however, is unable, even at 10 mM, to fully inhibit pyruvate oxidation. Concentrations of VPA higher than 1 mM have an uncoupling effect on mitochondrial respiration. The oxidation of other mitochondrial substrates such as isocitrate, 2-ketoglutarate, DL-3-hydroxybutyrate and succinate is uncoupled but not inhibited by VPA. The effects of VPA on mitochondrial metabolism may be related to the therapeutic and/or toxicologic properties of this drug.
抗惊厥药物丙戊酸可竞争性抑制大鼠脑和肝线粒体中的丙酮酸载体。由于这种抑制作用，丙酮酸氧化所支持的氧消耗也会受到影响。在我们的实验条件下，低至0.05 mM的丙戊酸浓度就能部分抑制丙酮酸氧化。然而，即使在10 mM时，丙戊酸也无法完全抑制丙酮酸氧化。高于1 mM的丙戊酸浓度会对线粒体呼吸产生解偶联作用。其他线粒体底物如异柠檬酸、2-酮戊二酸、DL-3-羟基丁酸和琥珀酸的氧化会被解偶联，但不会被丙戊酸抑制。丙戊酸对线粒体代谢的影响可能与其治疗和/或毒理学特性有关。
