Suppr超能文献

芥酰肉碱对大鼠心脏线粒体抑制作用机制的研究。

Studies on the mechanism of the inhibitory effects of erucylcarnitine in rat heart mitochondria.

作者信息

Christophersen B O, Christiansen R Z

出版信息

Biochim Biophys Acta. 1975 Jun 23;388(3):402-12. doi: 10.1016/0005-2760(75)90099-5.

Abstract
  1. The mechanism of the inhibitory effect of erucylcarnitine on palmityl-carnitine oxidation in rat heart mitochondria was studied. 2. Erucylcarnitine inhibited in the same time the oxidation of [U-14-C]-palmitylcarnitine and the total rate of oxygen uptake. Other acylcarnitines competed as well for the oxidation with radioactive palmitylcarnitine, but they were well oxidized themselves, so that the total oxygen uptake did not decrease. 3. The presence of erucylcarnitine did not change the distribution pattern of Krebs cycle intermediates derived from [U-minus 14 C] palmitylcarnitine except that succinate/malate ratio increased. 4. The presence of erucylcarnitine did not lead to the formation of any beta-oxidation cycle intermediates from [U-minus 14 C] palymitylcarnitine. The formation of beta-hydroxy-palmityl derivative when rotenon was included into the incubation medium, decreased in the presence of erucylcarnitine. 5. It is postulated, that the inhibited entrance of palmityl groups into the beta-oxidation cycle is due to the fact that erucylcarnitine and palmitylcarnitine behave as substrate-competitive inhibitors for long chain acyl-CoA dehydrogenase. 6. There was observed a latency of 1-2 min in the effect of erucylcarnitine on the palmitylcarnitine oxidation, which seems to correspond to the time required for the formation of high amounts of intramitochondrial erucyl-CoA. 7. Erucylcarnitine inhibited the total oxygen uptake with long, medium and short chain acylcarnitines, pyruvate and alpha-ketoglutarate as substrates, while the oxidation of succinate was not affected. 8. Sequestration of free CoA in the form of very slowly metabolized erucyl-CoA is proposed as the partial explanation of the observed inhibitory effects of erucylcarnitine on the oxidation of CoA-dependent substrates (alternatively to the inhibition at the level of acyl-CoA dehydrogenases in case of acylcarnitines).
摘要
  1. 研究了芥酰肉碱对大鼠心脏线粒体中棕榈酰肉碱氧化的抑制作用机制。2. 芥酰肉碱同时抑制了[U-14-C]-棕榈酰肉碱的氧化以及总氧摄取率。其他酰基肉碱也与放射性棕榈酰肉碱竞争氧化,但它们自身能很好地被氧化,因此总氧摄取量并未降低。3. 芥酰肉碱的存在并未改变源自[U-14 C]棕榈酰肉碱的三羧酸循环中间产物的分布模式,只是琥珀酸/苹果酸比值增加。4. 芥酰肉碱的存在并未导致[U-14 C]棕榈酰肉碱形成任何β-氧化循环中间产物。当在孵育介质中加入鱼藤酮时,β-羟基棕榈酰衍生物的形成在芥酰肉碱存在时减少。5. 据推测,棕榈酰基团进入β-氧化循环受到抑制是因为芥酰肉碱和棕榈酰肉碱对长链酰基辅酶A脱氢酶表现为底物竞争性抑制剂。6. 观察到芥酰肉碱对棕榈酰肉碱氧化的作用有1 - 2分钟的延迟,这似乎与形成大量线粒体内芥酰辅酶A所需的时间相对应。7. 芥酰肉碱以长链、中链和短链酰基肉碱、丙酮酸和α-酮戊二酸为底物时抑制总氧摄取,而琥珀酸的氧化不受影响。8. 提出以代谢非常缓慢的芥酰辅酶A形式螯合游离辅酶A是对观察到的芥酰肉碱对依赖辅酶A的底物氧化的抑制作用的部分解释(对于酰基肉碱而言,这是在酰基辅酶A脱氢酶水平抑制的替代解释)。

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验