(R)-4,8-dimethylnonanoylcarnitine

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: (R)-4,8-dimethylnonanoylcarnitine
• 英文别名: (3R)-3-(4,8-dimethylnonanoyloxy)-4-(trimethylazaniumyl)butanoate
• 化学式: C18H35NO4
• 分子量: 329.5
• InChiKey: DDTDJDZHDFMZED-OEMAIJDKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  23
• 可旋转键数：
  12
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  66.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  左旋肉碱 、 4,8-dimethylnonanoyl-CoA(4-) 生成 coenzyme A 、 (R)-4,8-dimethylnonanoylcarnitine
  参考文献：
  名称：

  人肉毒碱辛酰基转移酶的分子克隆和表达：证明其在支链脂肪酸的过氧化物酶体β-氧化中的作用。

  摘要：

  为了研究人肉碱辛酰基转移酶（COT）在支链脂肪酸的β-氧化中的假定作用，我们鉴定并克隆了编码人COT的cDNA，并在酿酒酵母中表达了它。酶活性测量表明，COT有效地将过氧体过氧化物酶体β-氧化的链烷酸4、8-二甲基壬酰基-CoA转化为其相应的肉碱酯。过氧化物酶体中该支链/中链酰基辅酶A的肉碱酯的生产需要其运输到线粒体，然后发生进一步的β-氧化。相反，4，8-二甲基壬酰基-CoA不是肉碱乙酰基转移酶的底物，肉碱乙酰基转移酶是位于过氧化物酶体中的另一种酰基转移酶，它催化了链烷酸β-氧化的其他产物肉碱酯的形成，即乙酰辅酶A和丙酰辅酶A。我们的研究结果揭示了COT在脂肪酸代谢中的功能，并指出了COT在支链脂肪酸的β-氧化中的关键作用。

  DOI：

  10.1006/bbrc.1999.1340

文献信息

• Carnitine palmitoyltransferase 2: New insights on the substrate specificity and implications for acylcarnitine profiling
  作者：Sara Violante、Lodewijk IJlst、Henk van Lenthe、Isabel Tavares de Almeida、Ronald J. Wanders、Fátima V. Ventura

  DOI：10.1016/j.bbadis.2010.06.002

  日期：2010.9

  were quantified by ESI-MS/MS. We show that CPT2 is active with medium (C8-C12) and long-chain (C14-C18) acyl-CoA esters, whereas virtually no activity was found with short- and very long-chain acyl-CoAs or with branched-chain amino acid oxidation intermediates. Trans-2-enoyl-CoA intermediates were also found to be poor substrates for CPT2. Inhibition studies performed revealed that trans-2-C16:1-CoA may

  近年来，酰基肉碱已成为诊断线粒体脂肪酸β-氧化（mFAO）和支链氨基酸氧化障碍的重要生物标志物，前提是它们反映了潜在的毒性酰基辅酶A物种，在线粒体内积累在酶嵌段的上游。但是，这些中间体的起源仍然知之甚少。肉碱航天飞机成员肉碱棕榈酰转移酶2（CPT2）可能参与了线粒体内由积累的酰基CoA代谢产物合成的酰基肉碱。为了解决这个问题，本文研究了CPT2的底物特异性概况。将表达人CPT2的啤酒酵母匀浆与饱和和不饱和的C2-C26酰基辅酶A和支链氨基酸氧化中间体孵育。通过ESI-MS / MS对产生的酰基肉碱进行定量。我们显示CPT2与中等（C8-C12）和长链（C14-C18）酰基辅酶A酯具有活性，而实际上未发现短链和长链酰基辅酶A或支链氨基具有活性酸氧化中间体。还发现反式-2-烯酰基-CoA中间体是CPT2的不良底物。进行的抑制研究表明，trans-2-C16：1-CoA可以作为CPT2的竞争性抑制剂（K（i）为18
• Substrate specificity of human carnitine acetyltransferase: Implications for fatty acid and branched-chain amino acid metabolism
  作者：Sara Violante、Lodewijk IJlst、Jos Ruiter、Janet Koster、Henk van Lenthe、Marinus Duran、Isabel Tavares de Almeida、Ronald J.A. Wanders、Sander M. Houten、Fátima V. Ventura

  DOI：10.1016/j.bbadis.2013.02.012

  日期：2013.6

  Carnitine acyltransferases catalyze the reversible conversion of acyl-CoAs into acylcarnitine esters. This family includes the mitochondrial enzymes carnitine palmitoyltransferase 2 (CPT2) and carnitine acetyltransferase (CrAT). CPT2 is part of the carnitine shuttle that is necessary to import fatty acids into mitochondria and catalyzes the conversion of acylcarnitines into acyl-CoAs. In addition, when mitochondrial fatty acid P-oxidation is impaired, CPT2 is able to catalyze the reverse reaction and converts accumulating long- and medium-chain acyl-CoAs into acylcarnitines for export from the matrix to the cytosol. However, CPT2 is inactive with short-chain acyl-CoAs and intermediates of the branched-chain amino acid oxidation pathway (BCAAO). In order to explore the origin of short-chain and branched-chain acylcarnitines that may accumulate in various organic acidemias, we performed substrate specificity studies using purified recombinant human CrAT. Various saturated, unsaturated and branched-chain acyl-CoA esters were tested and the synthesized acylcarnitines were quantified by ESI-MS/MS. We show that CrAT converts short- and medium-chain acyl-CoAs (C2 to C10-00A), whereas no activity was observed with long-chain species. Trans-2-enoyl-00A intermediates were found to be poor substrates for this enzyme. Furthermore, CrAT turned out to be active towards some but not all the BCAAO intermediates tested and no activity was found with dicarboxylic acyl-CoA esters. This suggests the existence of another enzyme able to handle the acyl-CoAs that are not substrates for CrAT and CPT2, but for which the corresponding acylcarnitines are well recognized as diagnostic markers in inborn errors of metabolism. (C) 2013 Elsevier B.V. All rights reserved.
• Molecular Cloning and Expression of Human Carnitine Octanoyltransferase: Evidence for Its Role in the Peroxisomal β-Oxidation of Branched-Chain Fatty Acids
  作者：Sacha Ferdinandusse、Joyce Mulders、Lodewijk IJlst、Simone Denis、Georges Dacremont、Hans R. Waterham、Ronald J.A. Wanders

  DOI：10.1006/bbrc.1999.1340

  日期：1999.9

  putative role of human carnitine octanoyltransferase (COT) in the beta-oxidation of branched-chain fatty acids, we identified and cloned the cDNA encoding human COT and expressed it in the yeast Saccharomyces cerevisiae. Enzyme activity measurements showed that COT efficiently converts one of the end products of the peroxisomal beta-oxidation of pristanic acid, 4, 8-dimethylnonanoyl-CoA, to its corresponding

  为了研究人肉碱辛酰基转移酶（COT）在支链脂肪酸的β-氧化中的假定作用，我们鉴定并克隆了编码人COT的cDNA，并在酿酒酵母中表达了它。酶活性测量表明，COT有效地将过氧体过氧化物酶体β-氧化的链烷酸4、8-二甲基壬酰基-CoA转化为其相应的肉碱酯。过氧化物酶体中该支链/中链酰基辅酶A的肉碱酯的生产需要其运输到线粒体，然后发生进一步的β-氧化。相反，4，8-二甲基壬酰基-CoA不是肉碱乙酰基转移酶的底物，肉碱乙酰基转移酶是位于过氧化物酶体中的另一种酰基转移酶，它催化了链烷酸β-氧化的其他产物肉碱酯的形成，即乙酰辅酶A和丙酰辅酶A。我们的研究结果揭示了COT在脂肪酸代谢中的功能，并指出了COT在支链脂肪酸的β-氧化中的关键作用。