Vamecq J
Biochem J. 1987 Feb 1;241(3):783-91. doi: 10.1042/bj2410783.
The enzyme targets for chlorpromazine inhibition of rat liver peroxisomal and mitochondrial oxidations of fatty acids were studied. Effects of chlorpromazine on total fatty acyl-CoA synthetase activity, on both the first and the third steps of peroxisomal beta-oxidation, on the entry of fatty acyl-CoA esters into the peroxisome and on catalase activity, which allows breakdown of the H2O2 generated during the acyl-CoA oxidase step, were analysed. On all these metabolic processes, chlorpromazine was found to have no inhibitory action. Conversely, peroxisomal carnitine octanoyltransferase activity was depressed by 0.2-1 mM-chlorpromazine, which also inhibits mitochondrial carnitine palmitoyltransferase activity in all conditions in which these enzyme reactions are assayed. Different patterns of inhibition by the drug were, however, demonstrated for both these enzyme activities. Inhibitory effects of chlorpromazine on mitochondrial cytochrome c oxidase activity were also described. Inhibitions of both cytochrome c oxidase and carnitine palmitoyltransferase are proposed to explain the decreased mitochondrial fatty acid oxidation with 0.4-1.0 mM-chlorpromazine reported by Leighton, Persico & Necochea [(1984) Biochem. Biophys. Res. Commun. 120, 505-511], whereas depression by the drug of carnitine octanoyltransferase activity is presented as the factor responsible for the decreased peroxisomal beta-oxidizing activity described by the above workers.
研究了氯丙嗪对大鼠肝脏过氧化物酶体和线粒体脂肪酸氧化的酶作用靶点。分析了氯丙嗪对总脂肪酰辅酶A合成酶活性、过氧化物酶体β氧化第一步和第三步、脂肪酰辅酶A酯进入过氧化物酶体以及过氧化氢酶活性（该酶可分解酰基辅酶A氧化酶步骤中产生的过氧化氢）的影响。结果发现，氯丙嗪对所有这些代谢过程均无抑制作用。相反，0.2 - 1 mM的氯丙嗪可降低过氧化物酶体肉碱辛酰转移酶的活性，在测定这些酶反应的所有条件下，氯丙嗪还可抑制线粒体肉碱棕榈酰转移酶的活性。然而，该药物对这两种酶活性的抑制模式不同。还描述了氯丙嗪对线粒体细胞色素c氧化酶活性的抑制作用。有人提出，细胞色素c氧化酶和肉碱棕榈酰转移酶的抑制作用可解释Leighton、Persico和Necochea [（1984年）《生物化学与生物物理学研究通讯》120，505 - 511]报道的0.4 - 1.0 mM氯丙嗪使线粒体脂肪酸氧化减少的现象，而该药物对肉碱辛酰转移酶活性的抑制作用则被认为是上述研究人员所描述的过氧化物酶体β氧化活性降低的原因。
