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硫代取代脂肪酸对线粒体和过氧化物酶体β-氧化的影响。体内和体外研究。

Effects of thia-substituted fatty acids on mitochondrial and peroxisomal beta-oxidation. Studies in vivo and in vitro.

作者信息

Hovik R, Osmundsen H, Berge R, Aarsland A, Bergseth S, Bremer J

机构信息

Department of Physiology and Biochemistry, Dental School, University of Oslo, Norway.

出版信息

Biochem J. 1990 Aug 15;270(1):167-73. doi: 10.1042/bj2700167.

Abstract
  1. The effects of 3-, 4- and 5-thia-substituted fatty acids on mitochondrial and peroxisomal beta-oxidation have been investigated. When the sulphur atom is in the 4-position, the resulting thia-substituted fatty acid becomes a powerful inhibitor of beta-oxidation. 2. This inhibition cannot be explained in terms of simple competitive inhibition, a phenomenon which characterizes the inhibitory effects of 3- and 5-thia-substituted fatty acids. The inhibitory sites for 4-thia-substituted fatty acids are most likely to be the acyl-CoA dehydrogenase in mitochondria and the acyl-CoA oxidase in peroxisomes. 3. The inhibitory effect of 4-thia-substituted fatty acids is expressed both in vitro and in vivo. The effect in vitro is instantaneous, with up to 95% inhibition of palmitoylcarnitine oxidation. The effect in vivo, in contrast, is dose-dependent and increases with duration of treatment. 4. Pretreatment of rats with a 3-thia-substituted fatty acid rendered mitochondrial beta-oxidation less sensitive to inhibition by 4-thia-substituted fatty acids.
摘要
  1. 研究了3-、4-和5-硫代取代脂肪酸对线粒体和过氧化物酶体β-氧化的影响。当硫原子处于4位时,生成的硫代取代脂肪酸成为β-氧化的强力抑制剂。2. 这种抑制作用不能用简单的竞争性抑制来解释,而3-和5-硫代取代脂肪酸的抑制作用具有这种特征。4-硫代取代脂肪酸的抑制位点最有可能是线粒体中的酰基辅酶A脱氢酶和过氧化物酶体中的酰基辅酶A氧化酶。3. 4-硫代取代脂肪酸的抑制作用在体外和体内均有表现。体外作用是即时的,对棕榈酰肉碱氧化的抑制率高达95%。相比之下,体内作用是剂量依赖性的,且随治疗持续时间增加。4. 用3-硫代取代脂肪酸预处理大鼠,使线粒体β-氧化对4-硫代取代脂肪酸的抑制作用不那么敏感。

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