(15Z)-tetracosenoate

• 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: (15Z)-tetracosenoate
• 英文别名: (Z)-tetracos-15-enoate
• 化学式: C24H45O2-
• 分子量: 365.6
• InChiKey: GWHCXVQVJPWHRF-KTKRTIGZSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  11.2
• 重原子数：
  26
• 可旋转键数：
  20
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  40.1
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  水 、 神经酸酰胺 生成 (15Z)-tetracosenoate 、 Sphingosine(1+)
  参考文献：
  名称：

  结核分枝杆菌的重组中性神经酰胺酶的表达，纯化和鉴定。

  摘要：

  神经酰胺酶（CDase）催化神经酰胺（Cer）水解为鞘氨醇（Sph）和脂肪酸。我们已经报道了分枝杆菌CDase（MtCDase）的分子克隆和初步表征（J.Biol.Chem。，274，36616-36622（1999））。为了进一步确定其功能，MtCDase在大肠杆菌中表达并通过Ni-Sepharose和凝胶过滤纯化。纯化的重组酶在SDS-PAGE上显示一条条带，分子量估计为71 kDa。它的最适pH为8.0-9.0，对各种Cers具有相当广泛的特异性。在测试的不同脂肪酸部分的Cer中，由C6-C24脂肪酸组成的Cer被很好地水解，具有单不饱和脂肪酸的Cer的水解程度远高于具有饱和脂肪酸的Cer。使用N-十二烷酰基-7-硝基苯-2-氧杂-1 以3-4-二唑（NBD）-D-赤型鞘氨醇（C12-NBD-Cer）为底物，反应遵循正常的Michaelis-Menten动力学。C12-NBD-Cer的表观Km和Vmax值分别为98

  DOI：

  10.1271/bbb.90645

文献信息

• Fatty acid amide hydrolase substrate specificity
  作者：Dale L Boger、Robert A Fecik、Jean E Patterson、Hiroshi Miyauchi、Matthew P Patricelli、Benjamin F Cravatt

  DOI：10.1016/s0960-894x(00)00528-x

  日期：2000.12

  Fatty acid amide hydrolase (FAAH), also referred to as oleamide hydrolase and anandamide amidohydrolase, is a serine hydrolase responsible for the degradation of endogenous oleamide and anandamide, fatty acid amides that function as chemical messengers. FAAH hydrolyzes a range of fatty acid amides, and the present study examines the relative rates of hydrolysis of a variety of natural and unnatural

  脂肪酸酰胺水解酶（FAAH），也称为油酰胺水解酶和阿南酰胺酰胺水解酶，是一种丝氨酸水解酶，负责降解内源性油酰胺和阿南酰胺（充当化学信使的脂肪酸酰胺）。FAAH水解多种脂肪酸酰胺，本研究使用纯重组大鼠FAAH检查了各种天然和非天然脂肪酸伯酰胺底物的相对水解速率。
• Biochemical characterization of the PHARC-associated serine hydrolase ABHD12 reveals its preference for very-long-chain lipids
  作者：Alaumy Joshi、Minhaj Shaikh、Shubham Singh、Abinaya Rajendran、Amol Mhetre、Siddhesh S. Kamat

  DOI：10.1074/jbc.ra118.005640

  日期：2018.11

  Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract (PHARC) is a rare genetic human neurological disorder caused by null mutations to the Abhd12 gene, which encodes the integral membrane serine hydrolase enzyme ABHD12. Although the role that ABHD12 plays in PHARC is understood, the thorough biochemical characterization of ABHD12 is lacking. Here, we report the facile synthesis of mono-1-(fatty)acyl-glycerol lipids of varying chain lengths and unsaturation and use this lipid substrate library to biochemically characterize recombinant mammalian ABHD12. The substrate profiling study for ABHD12 suggested that this enzyme requires glycosylation for optimal activity and that it has a strong preference for very-long-chain lipid substrates. We further validated this substrate profile against brain membrane lysates generated from WT and ABHD12 knockout mice. Finally, using cellular organelle fractionation and immunofluorescence assays, we show that mammalian ABHD12 is enriched on the endoplasmic reticulum membrane, where most of the very-long-chain fatty acids are biosynthesized in cells. Taken together, our findings provide a biochemical explanation for why very-long-chain lipids (such as lysophosphatidylserine lipids) accumulate in the brains of ABHD12 knockout mice, which is a murine model of PHARC.
• Assignment of Endogenous Substrates to Enzymes by Global Metabolite Profiling
  作者：Alan Saghatelian、Sunia A. Trauger、Elizabeth J. Want、Edward G. Hawkins、Gary Siuzdak、Benjamin F. Cravatt

  DOI：10.1021/bi0480335

  日期：2004.11.1

  Enzymes regulate biological processes through the conversion of specific substrates to products. Therefore, of fundamental interest for every enzyme is the elucidation of its natural substrates. Here, we describe a general strategy for identifying endogenous substrates of enzymes by untargeted liquid chromatography-mass spectrometry (LC-MS) analysis of tissue metabolomes from wild-type and enzyme-inactivated organisms. We use this method to discover several brain lipids regulated by the mammalian enzyme fatty acid amide hydrolase (FAAH) in vivo, including known signaling molecules (e.g., the endogenous cannabinoid anandamide) and a novel family of nervous system-enriched natural products, the taurine-conjugated fatty acids. Remarkably, the relative hydrolytic activity that FAAH exhibited for lipid metabolites in vitro was not predictive of the identity of specific FAAH substrates in vivo. Thus, global metabolite profiling establishes unanticipated connections between the proteome and metabolome that enable assignment of an enzyme's unique biochemical functions in vivo.
• Biochemical Characterization of the Reverse Activity of Rat Brain Ceramidase
  作者：Samer El Bawab、Helene Birbes、Patrick Roddy、Zdzislaw M. Szulc、Alicja Bielawska、Yusuf A. Hannun

  DOI：10.1074/jbc.m009331200

  日期：2001.5

  We have previously purified a membrane-bound ceramidase from rat brain and recently cloned the human homologue, We also observed that the same enzyme is able to catalyze the reverse reaction of ceramide synthesis. To obtain insight into the biochemistry of this enzyme, we characterized in this study this reverse activity. Using sphingosine and palmitic acid as substrates, the enzyme exhibited Michaelis-Menten kinetics; however, the enzyme did not utilize palmitoyl-CoA as substrate. Also, the activity was not inhibited in vitro and in cells by fumonisin B-1, an inhibitor of the CoA-dependent ceramide synthase, The enzyme showed a narrow pH optimum in the neutral range, and there was very low activity in the alkaline range. Substrate specificity studies were performed, and the enzyme showed the highest activity with D-erythro-sphingosine (K-m of 0.16 mol %, and V-max of 0.3 mu mol/min/mg), but D-erythro-dihydrosphingosine and the three unnatural stereoisomers of sphingosine were poor substrates. The specificity for the fatty acid was also studied, and the highest activity was observed for myristic acid with a K-m of 1.7 mol % and a V-max of 0.63 mu mol/min/mg, Kinetic studies were performed to investigate the mechanism of the reaction, and Lineweaver-Burk plots indicated a sequential mechanism. Two competitive inhibitors of the two substrates were identified, L-erythro-sphingosine and myristaldehyde, and inhibition studies indicated that the reaction followed a random sequential mechanism. The effect of lipids were also tested. Most of these lipids showed moderate inhibition, whereas the effects of phosphatidic acid and cardiolipin were more potent with total inhibition at around 2.5-5 mol %, Paradoxically, cardiolipin stimulated ceramidase activity. These results define the biochemical characteristics of this reverse activity. The results are discussed in view of a possible regulation of this enzyme by the intracellular pH or by an interaction with cardiolipin and/or phosphatidic acid.
• Golgi alkaline ceramidase regulates cell proliferation and survival by controlling levels of sphingosine and S1P
  作者：Ruijuan Xu、Junfei Jin、Wei Hu、Wei Sun、Jacek Bielawski、Zdzislaw Szulc、Tarek Taha、Lina M. Obeid、Cungui Mao

  DOI：10.1096/fj.05-5689com

  日期：2006.9

  Sphingosine-1-phosphate (S1P), a sphingolipid metabolite, promotes cell proliferation and survival whereas its precursor, sphingosine, has the opposite effects. However, much remains unknown about their regulation. Here we identify a novel human ceramidase (haCER2) that regulates the levels of both sphingosine and S1P by controlling the hydrolysis of ceramides. haCER2 is localized to the Golgi complex and is highly expressed in the placenta. High ectopic expression of haCER2 caused fragmentation of the Golgi complex and growth arrest in HeLa cells due to sphingosine accumulation. Low ectopic expression of haCER2 increased S1P without sphingosine accumulation, promoting cell proliferation in serum-free medium. This proliferative effect was suppressed by dimethylsphingosine, an inhibitor of the S1P formation, or by the RNA interference (RNAi) - mediated inhibition of S1P(1), a G-protein-coupled receptor for S1P. The RNAi-mediated down-regulation of haCER2 enhanced the serum deprivation-induced growth arrest and apoptosis of HeLa cells, which was inhibited by addition of exogenous S1P. Serum deprivation up-regulated both haCER2 mRNA and activity in HeLa cells. haCER2 mRNA is also up-regulated in some tumors. Taken together, these results suggest that haCER2 is important for the generation of S1P and S1P-mediated cell proliferation and survival, but that its overexpression may cause cell growth arrest due to an accumulation of sphingosine. - Xu, R., Jin, J., Hu, W., Sun, W., Bielawski, J., Szulc, Z., Taha, T., Obeid, L. M., Mao, C. Golgi alkaline ceramidase regulates cell proliferation and survival by controlling levels of sphingosine and S1P