hexadecanoyl CoA | 1763-10-6

• 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: hexadecanoyl CoA
• 英文别名: [(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-2-[[[[(3R)-4-[[3-(2-hexadecanoylsulfanylethylamino)-3-oxopropyl]amino]-3-hydroxy-2,2-dimethyl-4-oxobutoxy]-oxidophosphoryl]oxy-oxidophosphoryl]oxymethyl]-4-hydroxyoxolan-3-yl] phosphate
• CAS: 1763-10-6
• 化学式: C37H62N7O17P3S-4
• 分子量: 1001.9
• InChiKey: MNBKLUUYKPBKDU-BBECNAHFSA-J

物化性质

• 密度：
  1.54±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  65
• 可旋转键数：
  33
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.78
• 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：

  1-O-palmitoyl-2-[(9z)-octadenoyl]-glycerol 、 hexadecanoyl CoA 生成 1,3棕榈酸-2-反油酸甘油酯 、 coenzyme A
  参考文献：
  名称：

  酰基辅酶A：单酰基甘油酰基转移酶3的鉴定，这是一种与饮食中脂肪吸收有关的肠道特异性酶。

  摘要：

  酰基辅酶A：单酰基甘油酰基转移酶（MGAT）使用2-单酰基甘油和脂肪酰基辅酶A催化二酰基甘油的合成。该酶促反应是小肠吸收脂肪的必不可少的限速步骤。尽管最近已分离出第一个编码MGAT的cDNA，称为MGAT1，但它并未在小肠中表达，因此无法解释高肠MGAT酶活性，这对脂肪吸收的生理至关重要。在当前的研究中，我们报告了一种新型MGAT的鉴定，命名为MGAT3，并提供证据表明它符合成为难以捉摸的肠道MGAT的标准。MGAT3编码与MGAT1和-2高度同源的约36 kDa跨膜蛋白。在人类中 MGAT3的表达仅限于在回肠中发现的最高水平的胃肠道。在细胞水平上，重组MGAT3定位于内质网。在昆虫Sf9细胞中产生的重组MGAT3酶活性比其他立体异构体具有更高的选择性选择性地酰化2-单酰基甘油。MGAT3的分子鉴定将有助于评估将肠道MGAT用作抗肥胖疗法的潜在干预点。

  DOI：

  10.1074/jbc.c300042200
• 作为产物：
  描述：

  (2R)-4-[[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-4-hydroxy-3-phosphonatooxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl]oxy-N-[3-[2-[(E)-hexadec-2-enoyl]sulfanylethylimino]-3-oxidopropyl]-2-hydroxy-3,3-dimethylbutanimidate 、 氢(+1)阳离子 、 NADH 生成 hexadecanoyl CoA 、 nicotinamide adenine dinucleotide
  参考文献：
  名称：

  Enzymic Characterization of the Target for Isoniazid in Mycobacterium tuberculosis

  摘要：

  The inhA gene has been recently shown to encode a common protein target for isoniazid and ethionamide action in Mycobacterium tuberculosis. In this paper, we demonstrate that the M. tuberculosis InhA protein catalyzes the NADH-specific reduction of 2-trans-enoyl-ACP, essential for fatty acid elongation. This enzyme preferentially reduces long-chain substrates (12-24 carbons), consistent with its involvement in mycolic acid biosynthesis. Steady-state kinetic studies showed that the two substrates bind to InhA via a sequential kinetic mechanism, with the preferred ordered addition of NADH and the enoyl substrate. The chemical mechanism involves stereospecific hydride transfer of the 4S hydrogen of NADH to the C-3 position of the 2-trans-enoyl substrate, followed by protonation at C-2 of an enzyme-stabilized enolate intermediate. Kinetic and microcalorimetric analysis demonstrates that the binding of NADH to the S94A mutant InhA, known to confer resistance to both isoniazid and ethionamide, is altered. This difference can account for the isoniazid-resistance phenotype, with the formation of a binary InhA-NADH complex required for drug binding. Isoniazid binding to either the wild-type or S94A mutant InhA could not be detected by titration microcalorimetry, suggesting that this compound is a prodrug, which must be converted to its active form.

  DOI：

  10.1021/bi00026a004

文献信息

• Characterization of an Acyl-CoA Thioesterase That Functions as a Major Regulator of Peroxisomal Lipid Metabolism
  作者：Mary C. Hunt、Karianne Solaas、B. Frode Kase、Stefan E.H. Alexson

  DOI：10.1074/jbc.m106458200

  日期：2002.1

  sequestration and to facilitate excretion of chain-shortened carboxylic acids, acyl-CoA thioesterases, which catalyze the hydrolysis of acyl-CoAs to the free acid and CoASH, may play important roles. Here we have cloned and characterized a peroxisomal acyl-CoA thioesterase from mouse, named PTE-2 (peroxisomal acyl-CoA thioesterase 2). PTE-2 is ubiquitously expressed and induced at mRNA level by treatment

  过氧化物酶体在极长链脂肪酸和长链脂肪酸，二羧酸脂肪酸，胆汁酸中间体，前列腺素，白三烯，血栓烷，pristanic酸和异种生物羧酸的β-氧化中起作用。这些脂质主要是作为羧酸排泄缩短链，或运输到线粒体进行进一步代谢。这些羧酸中的几种被缓慢氧化，因此可能螯合辅酶A（CoASH）。为防止CoASH螯合并促进链缩短的羧酸的排泄，可催化酰基CoA水解为游离酸和CoASH的酰基CoA硫酯酶可能起重要作用。在这里，我们从小鼠克隆并表征了过氧化物酶体酰基辅酶A硫酯酶，称为PTE-2（过氧化物酶体酰基辅酶A硫酯酶2）。通过用过氧化物酶体增殖物WY-14643处理和禁食，PTE-2在mRNA水平普遍表达和诱导。这些治疗方法所见的诱导作用取决于过氧化物酶体增殖物激活的受体α。重组PTE-2对酰基辅酶A表现出宽的链长特异性，从短链，中链到长链酰基辅酶A，以及其他底物，包括三羟基辅前列腺酸辅酶A，羟甲基戊二酰辅酶A和
• 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
• Utilization of Sterol Carrier Protein-2 by Phytanoyl-CoA 2-Hydroxylase in the Peroxisomal α Oxidation of Phytanic Acid
  作者：Mridul Mukherji、Nadia J. Kershaw、Christopher J. Schofield、Anthony S. Wierzbicki、Matthew D. Lloyd

  DOI：10.1016/s1074-5521(02)00139-4

  日期：2002.5

  first step of which is catalyzed by phytanoyl-CoA 2-hydroxylase (PAHX). Mutations in human PAHX cause phytanic acid accumulations leading to Adult Refsum's Disease (ARD), which is also observed in a sterol carrier protein 2 (SCP-2)-deficient mouse model. Phytanoyl-CoA is efficiently 2-hydroxylated by PAHX in vitro in the presence of mature SCP-2. Other straight-chain fatty acyl-CoA esters were also 2-hydroxylated

  由于植烷酸具有3-甲基，因此可通过过氧化物酶体α-氧化途径降解植酸，其第一步是通过植烷酰辅酶A 2-羟化酶（PAHX）催化。人PAHX中的突变会导致植酸积累，从而导致成人Refsum's病（ARD），在缺乏固醇载体蛋白2（SCP-2）的小鼠模型中也观察到了这种现象。在成熟的SCP-2存在下，苯甲酰辅酶A在体外被PAHX有效地2-羟基化。其他直链脂肪酰基辅酶A酯也被2-羟基化，产物被分离和表征。SCP-2的使用增加了PAHX对直链（如十六烷酰-CoA）和支链（如植烷酰-CoA）底物的区分。
• Mutations in the Yeast LCB1 and LCB2Genes, Including Those Corresponding to the Hereditary Sensory Neuropathy Type I Mutations, Dominantly Inactivate Serine Palmitoyltransferase
  作者：Ken Gable、Gongshe Han、Erin Monaghan、Dagmar Bacikova、Mukil Natarajan、Robert Williams、Teresa M. Dunn

  DOI：10.1074/jbc.m107873200

  日期：2002.3

  mutated Lcb1p proteins retain their ability to interact with Lcb2p. Modeling studies suggest that serine palmitoyltransferase is likely to have a single active site that lies at the Lcb1p small middle dotLcb2p interface and that the mutations in Lcb1p reside near the lysine in Lcb2p that is expected to form the Schiff's base with the pyridoxal 5'-phosphate cofactor. Furthermore, mutations in this lysine

  最近证明，人SPTLC1基因中的突变编码丝氨酸棕榈酰转移酶（SPT）的Lcb1p亚基，可引起I型遗传感觉神经病。作为吡ido醛5'-磷酸酶亚家族的成员，称为α-氧胺合酶，丝氨酸棕榈酰转移酶催化鞘脂合成的重要步骤。被突变以引起I型遗传感觉神经病的残基位于Lcb1p的高度保守区域，根据与α-氧胺合成酶家族其他成员的比对，该区域预计是Lcb1p的催化结构域。我们发现啤酒酵母LCB1基因中的相应突变降低了丝氨酸棕榈酰转移酶的活性。当野生型和突变型LCB1等位基因共表达时，这些突变占优势，并使丝氨酸棕榈酰转移酶活性降低50％。我们还表明，丝氨酸棕榈酰转移酶是一个Lcb1p小中间点Lcb2p异二聚体，并且突变的Lcb1p蛋白保留了它们与Lcb2p相互作用的能力。建模研究表明，丝氨酸棕榈酰转移酶可能具有一个位于Lcb1p小中间点dotLcb2p界面的单一活性位点，并且Lcb1p中的突变位于Lcb2p中的
• Identification of small subunits of mammalian serine palmitoyltransferase that confer distinct acyl-CoA substrate specificities
  作者：Gongshe Han、Sita D. Gupta、Kenneth Gable、Somashekarappa Niranjanakumari、Prasun Moitra、Florian Eichler、Robert H. Brown、Jeffrey M. Harmon、Teresa M. Dunn

  DOI：10.1073/pnas.0811269106

  日期：2009.5.19

  Serine palmitoyltransferase (SPT) catalyzes the first committed step in sphingolipid biosynthesis. In yeast, SPT is composed of a heterodimer of 2 highly-related subunits, Lcb1p and Lcb2p, and a third subunit, Tsc3p, which increases enzyme activity markedly and is required for growth at elevated temperatures. Higher eukaryotic orthologs of Lcb1p and Lcb2p have been identified, but SPT activity is not highly correlated with coexpression of these subunits and no ortholog of Tsc3p has been identified. Here, we report the discovery of 2 proteins, ssSPTa and ssSPTb, which despite sharing no homology with Tsc3p, each substantially enhance the activity of mammalian SPT expressed in either yeast or mammalian cells and therefore define an evolutionarily conserved family of low molecular weight proteins that confer full enzyme activity. The 2 ssSPT isoforms share a conserved hydrophobic central domain predicted to reside in the membrane, and each interacts with both hLCB1 and hLCB2 as assessed by positive split ubiquitin 2-hybrid analysis. The presence of these small subunits, along with 2 hLCB2 isofoms, suggests that there are 4 distinct human SPT isozymes. When each SPT isozyme was expressed in either yeast or CHO LyB cells lacking endogenous SPT activity, characterization of their in vitro enzymatic activities, and long-chain base (LCB) profiling revealed differences in acyl-CoA preference that offer a potential explanation for the observed diversity of LCB seen in mammalian cells.

  丝氨酸棕榈酰转移酶（SPT）催化鞘脂生物合成的第一个承诺步骤。在酵母中，SPT由两个高度相关的亚基Lcb1p和Lcb2p的异二聚体以及第三个亚基Tsc3p组成，后者显著增加酶活性并且在高温下生长所必需。已经鉴定了Lcb1p和Lcb2p的高等真核生物同源物，但SPT活性与这些亚基的共表达并不高度相关，并且没有Tsc3p的同源物被鉴定出来。在这里，我们报告了2种蛋白质，ssSPTa和ssSPTb，它们与Tsc3p没有任何同源性，但是在酵母或哺乳动物细胞中表达的哺乳动物SPT的活性都显著增强，因此定义了一类进化保守的低分子量蛋白，赋予完全的酶活性。这两种ssSPT亚型共享一个保守的疏水性中央区域，预测存在于膜中，并且每种亚型都与hLCB1和hLCB2相互作用，通过阳性分裂泛素2杂交分析进行评估。这些小亚基的存在，以及2个hLCB2同工异构体，表明存在4种不同的人类SPT同功酶。当每种SPT同功酶在缺乏内源SPT活性的酵母或CHO LyB细胞中表达时，对它们的体外酶活性和长链碱基（LCB）分析的表征揭示了酰辅酶A偏好的差异，这提供了一个潜在的解释，用于解释哺乳动物细胞中观察到的LCB的多样性。