Cerotate

• 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: Cerotate
• 英文别名: hexacosanoate
• 化学式: C26H51O2-
• 分子量: 395.7
• InChiKey: XMHIUKTWLZUKEX-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  12.4
• 重原子数：
  28
• 可旋转键数：
  23
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.96
• 拓扑面积：
  40.1
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  聚甘氨酸 、 Cerotate 生成 水 、 N-hexacosanoylglycinate
  参考文献：
  名称：

  摘要：

  DOI：
• 作为产物：
  描述：

  水 、 hexacosanoic acid (2,3-dihydroxy-1-hydroxymethyl-heptadecyl) amide 生成 Phytosphingosine(1+) 、 Cerotate
  参考文献：
  名称：

  Cloning of an Alkaline Ceramidase from Saccharomyces cerevisiae

  摘要：

  Ceramide is not only a core intermediate of sphingolipids but also an important modulator of many cellular events including apoptosis, cell cycle arrest, senescence, differentiation, and stress responses. Its turnover may be tightly regulated. However, little is known about the regulation of its metabolism because most enzymes responsible for its synthesis and breakdown have yet to be cloned. Here we report the cloning and characterization of the yeast gene YPC1 (YBR183w) by screening Saccharomyces cerevisiae genes whose overexpression bestows resistance to fumonisin B1. We demonstrate that the yeast gene YPC1 encodes an alkaline ceramidase activity responsible for the breakdown of dihydroceramide and phytoceramide but not unsaturated ceramide. YPC1 ceramidase activity was confirmed by in vitro studies using an Escherichia coli expression system. Importantly, YPC1p also has reverse activity, catalyzing synthesis of phytoceramide from palmitic acid and phytosphingosine. This ceramide synthase activity is CoA-independent and is resistant to fumonisin B1, thus explaining why YPC1 was cloned as a fumonisin B1-resistant gene.

  DOI：

  10.1074/jbc.275.10.6876

文献信息

• The Human Bile Acid-CoA:Amino Acid N-Acyltransferase Functions in the Conjugation of Fatty Acids to Glycine
  作者：James O'Byrne、Mary C. Hunt、Dilip K. Rai、Masayumi Saeki、Stefan E.H. Alexson

  DOI：10.1074/jbc.m300987200

  日期：2003.9

  Bile acid-CoA:amino acid N-acyltransferase (BACAT) catalyzes the conjugation of bile acids to glycine and taurine for excretion into bile. By use of site-directed mutagenesis and sequence comparisons, we have identified Cys-235, Asp-328, and His-362 as constituting a catalytic triad in human BACAT (hBACAT) and identifying BACAT as a member of the type I acyl-CoA thioesterase gene family. We therefore

  胆汁酸-CoA：氨基酸N-酰基转移酶（BACAT）催化胆汁酸与甘氨酸和牛磺酸的结合，从而排泄到胆汁中。通过使用定点诱变和序列比较，我们已鉴定出Cys-235，Asp-328和His-362构成人BACAT（hBACAT）中的催化三联体，并将BACAT鉴定为I型酰基辅酶A硫酯酶基因家族。因此，我们假设hBACAT也可能将脂肪酰基辅酶A和/或共轭脂肪酸水解为甘氨酸。我们在这里显示重组hBACAT也可以水解长链和非常长链的饱和酰基CoAs（主要是C16：0-C26：0），并且通过质谱法验证了hBACAT还可以将脂肪酸缀合到甘氨酸上。组织表达研究表明，BACAT在肝，胆囊以及近端和远端肠中都有强表达。然而，BACAT还可以在与胆汁酸形成和运输无关的多种组织中表达，这表明在调节长链脂肪酸的细胞内水平方面也起着重要的作用。在人皮肤成纤维细胞中的绿色荧光蛋白定位实验表明，hBACAT酶主要是胞质的。因此
• Molecular Cloning and Characterization of Two Mouse Peroxisome Proliferator-activated Receptor α (PPARα)-regulated Peroxisomal Acyl-CoA Thioesterases
  作者：Maria A.K. Westin、Stefan E.H. Alexson、Mary C. Hunt

  DOI：10.1074/jbc.m313863200

  日期：2004.5

  long- and very long-chain acyl-CoAs, bile acid-CoA intermediates, prostaglandins, leukotrienes, thromboxanes, dicarboxylic fatty acids, pristanic acid, and xenobiotic carboxylic acids. The very long- and long-chain acyl-CoAs are mainly chain-shortened and then transported to mitochondria for further metabolism. We have now identified and characterized two peroxisomal acyl-CoA thioesterases, named PTE-Ia

  过氧化物酶体是在长链和超长链酰基辅酶A，胆汁酸辅酶A中间体，前列腺素，白三烯，血栓烷，二羧酸脂肪酸，链烷酸和异种生物羧酸的β-氧化中起作用的细胞器。非常长和很长链的酰基辅酶A主要被链缩短，然后被运输到线粒体进行进一步的代谢。我们现已鉴定出两种过氧化物酶体酰基辅酶A硫酯酶，称为PTE-Ia和PTE-Ic，它们将酰基辅酶A水解为游离脂肪酸和辅酶A.PTE-Ia和PTE-Ic在酶切位点显示82％的序列同一性氨基酸水平和推定的-AKL过氧化物酶体1型靶向信号在两种蛋白的羧基末端均已鉴定。使用绿色荧光融合蛋白的定位实验显示PTE-1a和PTE-1c定位在过氧化物酶体中。尽管它们具有高水平的序列同一性，但我们显示PTE-Ia主要在长链酰基辅酶A上有活性，而PTE-Ic主要在中链酰基辅酶A上有活性。游离CoASH缺乏对酶活性的调节表明PTE-Ia和PTE-Ic调节过氧化物酶体内部的酰基辅酶A水平，并且它
• Human Liver-Specific Very-Long-Chain Acyl-Coenzyme A Synthetase: cDNA Cloning and Characterization of a Second Enzymatically Active Protein
  作者：Steven J. Steinberg、Susan J. Wang、Martina C. McGuinness、Paul A. Watkins

  DOI：10.1006/mgme.1999.2883

  日期：1999.9

  previously cloned two human genes encoding proteins homologous to rat peroxisomal VLCS; one (hVLCS) is the human ortholog to the rat VLCS gene and another (hVLCS-H1) encodes a related heart-specific protein. Here, we report the cloning of a third gene (hVLCS-H2) and characterization of its protein product. The hVLCS-H2 gene is located on human chromosome 19 and encodes a 690-amino-acid protein. The amino

  由酰基辅酶A（酰基辅酶A）合成酶催化的脂肪酸的活化是其后续代谢所必需的。过氧化物酶体和微粒体包含能够激活链长为22个或更多碳原子的脂肪酸的超长链酰基辅酶A合成酶（VLCS）。过氧化物酶体VLCS活性的下降部分是造成X连锁肾上腺皮质营养不良（X-ALD）的生化病理的原因，这说明VLCS在细胞脂肪酸稳态中的重要性。我们先前克隆了两个人类基因，它们编码与大鼠过氧化物酶体VLCS同源的蛋白质。一个（hVLCS）是大鼠VLCS基因的人类直系同源物，另一个（hVLCS-H1）编码相关的心脏特异性蛋白。在这里，我们报告第三个基因（hVLCS-H2）的克隆及其蛋白质产物的表征。hVLCS-H2基因位于人类19号染色体上，编码690个氨基酸的蛋白质。hVLCS-H2的氨基酸序列与hVLCS和hVLCS-H1的氨基酸序列相同，分别为44-45％和67-69％。瞬时过表达hVLCS-H2的COS-1细胞以非常长的1
• Dissecting the Role of Critical Residues and Substrate Preference of a Fatty Acyl-CoA Synthetase (FadD13) of Mycobacterium tuberculosis
  作者：Garima Khare、Vibha Gupta、Rakesh K. Gupta、Radhika Gupta、Rajiv Bhat、Anil K. Tyagi

  DOI：10.1371/journal.pone.0008387

  日期：——

  Newly emerging multi-drug resistant strains of Mycobacterium tuberculosis (M.tb) severely limit the treatment options for tuberculosis (TB); hence, new antitubercular drugs are urgently needed. The mymA operon is essential for the virulence and intracellular survival of M.tb and thus represents an attractive target for the development of new antitubercular drugs. This study is focused on the structure-function relationship of Fatty Acyl-CoA Synthetase (FadD13, Rv3089) belonging to the mymA operon. Eight site-directed mutants of FadD13 were designed, constructed and analyzed for the structural-functional integrity of the enzyme. The study revealed that mutation of Lys487 resulted in ∼95% loss of the activity thus demonstrating its crucial requirement for the enzymatic activity. Comparison of the kinetic parameters showed the residues Lys172 and Ala302 to be involved in the binding of ATP and Ser404 in the binding of CoenzymeA. The influence of mutations of the residues Val209 and Trp377 emphasized their importance in maintaining the structural integrity of FadD13. Besides, we show a synergistic influence of fatty acid and ATP binding on the conformation and rigidity of FadD13. FadD13 represents the first Fatty Acyl-CoA Synthetase to display biphasic kinetics for fatty acids. FadD13 exhibits a distinct preference for C26/C24 fatty acids, which in the light of earlier reported observations further substantiates the role of the mymA operon in remodeling the cell envelope of intracellular M.tb under acidic conditions. A three-dimensional model of FadD13 was generated; the docking of ATP to the active site verified its interaction with Lys172, Ala302 and Lys487 and corresponded well with the results of the mutational studies. Our study provides a significant understanding of the FadD13 protein including the identification of residues important for its activity as well as in the maintenance of structural integrity. We believe that the findings of this study will provide valuable inputs in the development of inhibitors against the mymA operon, an important target for the development of antitubercular drugs.

  新型抗结核药物。
• ω-Oxidation of Very Long-chain Fatty Acids in Human Liver Microsomes
  作者：Robert-Jan Sanders、Rob Ofman、Marinus Duran、Stephan Kemp、Ronald J.A. Wanders

  DOI：10.1074/jbc.m513481200

  日期：2006.5

  X-linked adrenoleukodystrophy ( X-ALD) is a severe neurodegenerative disorder biochemically characterized by elevated levels of very long-chain fatty acids ( VLCFA). Excess levels of VLCFAs are thought to play an important role in the pathogenesis of X-ALD. Therefore, therapeutic approaches for X-ALD are focused on the reduction or normalization of VLCFAs. In this study, we investigated an alternative oxidation route for VLCFAs, namely omega-oxidation. The results described in this study show that VLCFAs are substrates for the omega-oxidation system in human liver microsomes. Moreover, VLCFAs were not only converted into omega-hydroxy fatty acids, but they were also further oxidized to dicarboxylic acids via cytochrome P450-mediated reactions. High sensitivity toward the specific P450 inhibitor 17-octadecynoic acid suggested that omega-hydroxylation of VLCFAs is catalyzed by P450 enzymes belonging to the CYP4A/F subfamilies. Studies with individually expressed human recombinant P450 enzymes revealed that two P450 enzymes, i.e. CYP4F2 and CYP4F3B, participate in the omega-hydroxylation of VLCFAs. Both enzymes belong to the cytochrome P450 4F subfamily and have a high affinity for VLCFAs. In summary, this study demonstrates that VLCFAs are substrates for the human omega-oxidation system, and for this reason, stimulation of the in vivo VLCFA omega-oxidation pathway may provide an alternative mode of treatment to reduce the levels of VLCFAs in patients with X-ALD.