Chlorpromazine and carnitine-dependency of rat liver peroxisomal beta-oxidation of long-chain fatty acids.
Chlorpromazine and carnitine-dependency of rat liver peroxisomal beta-oxidation of long-chain fatty acids.
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DOI：
10.1042/bj2410783
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发表时间：
1987-02
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影响因子：
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通讯作者：
J. Vamecq
中科院分区：
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作者：
J. Vamecq
研究了氯丙嗪抑制大鼠肝过氧化物酶体和线粒体脂肪酸氧化的酶靶点。氯丙嗪对总脂肪酰辅酶A合成酶活性的影响，对过氧化物酶体β-氧化的第一和第三步，对进入过氧化物酶体的脂肪酰辅酶A酯和过氧化氢酶活性，这使得在酰基辅酶A氧化酶步骤中产生的过氧化氢的分解，进行了分析。对所有这些代谢过程，发现氯丙嗪没有抑制作用。相反，过氧化物酶体肉毒碱辛酰转移酶活性被0.2-1 mM-氯丙嗪抑制，这也抑制线粒体肉毒碱棕榈酰转移酶活性在所有条件下，这些酶的反应进行了测定。然而，这两种酶的活性都表现出不同的药物抑制模式。氯丙嗪对线粒体细胞色素c氧化酶活性的抑制作用也进行了描述。细胞色素c氧化酶和肉毒碱棕榈酰转移酶的抑制被提出来解释Leighton，Mr.C.& Necochea报道的用0.4-1.0 mM-氯丙嗪降低的线粒体脂肪酸氧化[（1984）Biochem. Biophys.通信资源120，505-511]，而肉毒碱辛酰基转移酶活性的药物抑制被认为是上述工作者描述的过氧化物酶体β-氧化活性降低的原因。
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.