2,6-dimethylheptanoyl-CoA(4-)

• 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: 2,6-dimethylheptanoyl-CoA(4-)
• 英文别名: [(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-2-[[[[(3R)-4-[[3-[2-(2,6-dimethylheptanoylsulfanyl)ethylamino]-3-oxopropyl]amino]-3-hydroxy-2,2-dimethyl-4-oxobutoxy]-oxidophosphoryl]oxy-oxidophosphoryl]oxymethyl]-4-hydroxyoxolan-3-yl] phosphate
• 化学式: C30H48N7O17P3S-4
• 分子量: 903.7
• InChiKey: GPXWBKWDXPBLKS-LNSOOWQSSA-J

计算性质

• 辛醇/水分配系数(LogP)：
  -2.7
• 重原子数：
  58
• 可旋转键数：
  24
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  400
• 氢给体数：
  5
• 氢受体数：
  22

反应信息

• 作为反应物：
  描述：

  左旋肉碱 、 2,6-dimethylheptanoyl-CoA(4-) 生成 coenzyme A 、 (R)-2,6-dimethylheptanoylcarnitine
  参考文献：
  名称：

  Substrate specificity of human carnitine acetyltransferase: Implications for fatty acid and branched-chain amino acid metabolism

  摘要：

  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.

  DOI：

  10.1016/j.bbadis.2013.02.012

文献信息

• Demonstration of Dimethylnonanoyl-CoA Thioesterase Activity in Rat Liver Peroxisomes Followed by Purification and Molecular Cloning of the Thioesterase Involved
  作者：R. Ofman、L. el Mrabet、G. Dacremont、D. Spijer、R.J.A. Wanders

  DOI：10.1006/bbrc.2001.6245

  日期：2002.1

  operational if peroxisomes contain 4,8-dimethylnonanoyl-CoA thioesterase activity. In this paper we show that rat liver peroxisomes indeed contain 4,8-dimethylnonanoyl-CoA thioesterase activity. We have partially purified the enzyme involved from peroxisomes and identified the protein as the rat ortholog of a known human thioesterase using MALDI-TOF mass spectrometry in combination with the rat EST database

  过氧化物酶体通过催化一组不同的脂肪酸和脂肪酸衍生物包括链烷酸（2,6,10,14-四甲基十五碳二烯酸）的链缩短，在高等真核生物中在细胞脂肪酸氧化中起着不可或缺的作用。较早的研究表明，豆蔻酸在过氧化物酶体中经历三个β氧化循环，生成4,8-二甲基壬酰基-CoA（DMN-CoA），然后转运至线粒体以完全氧化为CO（2）和H（2）哦 原则上，这可以通过两种不同的机制完成，其中DMN-CoA要么转化成相应的肉碱酯，要么水解成4,8-二甲基壬酸加CoASH。仅在过氧化物酶体具有4,8-二甲基壬酰基-CoA硫酯酶活性的情况下，后一种途径才有效。在本文中，我们表明大鼠肝脏过氧化物酶体确实含有4,8-二甲基壬酰基-CoA硫酯酶活性。我们已部分纯化过氧化物酶体中涉及的酶，并使用MALDI-TOF质谱结合大鼠EST数据库，将该蛋白鉴定为已知人硫酯酶的大鼠直系同源物。大肠杆菌中的异源表达研究确定该酶不仅水解DMN
• 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.