16-hydroxypalmitate

• 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: 16-hydroxypalmitate
• 英文别名: ω-1 hydroxypalmitate；16-hydroxyhexadecanoate
• 化学式: C₁₆H₃₁O₃
• 分子量: 271.42
• InChiKey: UGAGPNKCDRTDHP-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  19
• 可旋转键数：
  14
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.94
• 拓扑面积：
  60.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  Feruloyl-CoA 、 16-hydroxypalmitate 生成 16-Feruloyloxypalmitate 、 coenzyme A
  参考文献：
  名称：

  Identification of an Arabidopsis Feruloyl-Coenzyme A Transferase Required for Suberin Synthesis    

  摘要：

  所有植物都会产生亚油酸，这是细胞壁的亲脂性屏障，可以控制水和溶质通量，限制病原体感染。通常将其描述为由多聚脂肪族和多聚芳香族结构域组成的异聚物。主要单体包括ω-羟基和α，ω-二羧酸脂肪酸，甘油和ferulate。尚未确定芳香族亚油酸途径的基因。在这里，我们证明拟南芥（Arabidopsis thaliana）基因AT5G41040，是酰基转移酶BAHD家族的成员，对于将ferulate合并到亚油酸中至关重要。在转化了AT5G41040启动子：YFP融合的拟南芥植株中，报告基因表达定位于正在经历亚油酸化的细胞层。AT5G41040敲除突变体几乎完全消除了与亚油酸相关的酯键ferulate。然而，at5g41040根表皮中亚油酸的经典层状结构未被破坏。at5g41040敲除突变体种子中ferulate的减少与含有ω-羟基基团的脂肪族单体的近似化学计量减少相关。重组AT5G41040p催化从feruloyl-辅酶A到ω-羟基脂肪酸和脂肪醇的酰基转移，证明该基因编码feruloyl转移酶。还研究了CYP86B1，一种细胞色素P450单加氧酶基因，其转录水平与AT5G41040表达相关。敲除和过表达证实CYP86B1是亚油酸中非常长链饱和α，ω-双功能脂肪族单体生物合成所需的氧化酶。cyp86b1敲除突变体的种子亚油酸组成令人惊讶地被未被取代的脂肪酸所主导，这些酸无法形成聚合键。综上所述，这些结果挑战了我们对亚油酸结构的当前看法，质疑了酯键ferulate作为必要组分的功能以及扩展的脂肪族聚酯的存在。

  DOI：

  10.1104/pp.109.144907
• 作为产物：
  描述：

  palmitate ion 在 heme domain of cytochrome P450 BM-3 (A328V) mutant 、 potassium carbonate 、 还原型辅酶II(NADPH)四钠盐 作用下， 生成 ω-2 hydroxypalmitate 、 ω-3 hydroxypalmitate 、 16-hydroxypalmitate
  参考文献：
  名称：

  P450BM-3 的单个活性位点突变显着增强了底物结合和产物形成速率

  摘要：

  识别细胞色素 P450 的关键结构特征对于理解这些重要的药物代谢酶的催化机制至关重要。细胞色素 P450BM-3 (BM-3) 是一种结构和机械 P450 模型，可催化脂肪酸的区域和立体选择性羟基化。最近的工作证明了水在 BM-3 机制中的重要性，而定点诱变有助于阐明底物识别、结合和产物形成的机制。确定在 BM-3 活性位点中起关键作用的氨基酸之一是丙氨酸 328，它位于 K 螺旋和 β 1-4 之间的环中。在 A328V BM-3 突变体中，与野生型酶相比，底物亲和力增加了 5-10 倍，周转数增加了 2-8 倍。与野生型酶不同，这种突变体是从由于较高的结合亲和力，大肠杆菌与内源性底物结合。对底物结合的天然 BMP 和 A328V 突变 BMP 的晶体结构的仔细检查表明，底物的定位在两种形式的酶中基本相同，两个缬氨酸甲基占据野生活性位点中存在的空隙型底物结合结构。

  DOI：

  10.1021/bi201099j

文献信息

• Retinoids, ω-hydroxyfatty acids and cytotoxic aldehydes as physiological substrates, and H₂-receptor antagonists as pharmacological inhibitors, of human class IV alcohol dehydrogenase
  作者：Abdellah Allali-Hassani、Josep M Peralba、Sı́lvia Martras、Jaume Farrés、Xavier Parés

  DOI：10.1016/s0014-5793(98)00374-3

  日期：1998.4.24

  Kinetic constants of human class IV alcohol dehydrogenase (σσ‐ADH) support a role of the enzyme in retinoid metabolism, fatty acid ω‐oxidation, and elimination of cytotoxic aldehydes produced by lipid peroxidation. Class IV is the human ADH form most efficient in the reduction of 4‐hydroxynonenal (k cat/K m: 39 500 mM−1 min−1). Class IV shows high activity with all‐trans‐retinol and 9‐cis‐retinol,

  人类 IV 类酒精脱氢酶 (σσ-ADH) 的动力学常数支持该酶在类视黄醇代谢、脂肪酸 ω-氧化和消除脂质过氧化产生的细胞毒性醛中的作用。IV 类是还原 4-羟基壬烯醛最有效的人类 ADH 形式（k cat/K m：39 500 mM-1 min-1）。IV类对全反式-视黄醇和9-顺-视黄醇显示出高活性，而13-顺-视黄醇不是底物而是抑制剂。全反式视黄酸和 13-顺式视黄酸都是视黄醇氧化的有效竞争性抑制剂 (K i: 3–10 μM)，可作为调节视黄酸生成和 13 -顺式异构体。乙醇对 IV 类视黄醇氧化的抑制 (K i: 6-10 mM) 可能是乙醇毒性和致畸作用的起源。
• A hydroxycinnamoyltransferase responsible for synthesizing suberin aromatics in <i>Arabidopsis</i>
  作者：Jin-Ying Gou、Xiao-Hong Yu、Chang-Jun Liu

  DOI：10.1073/pnas.0905555106

  日期：2009.11.3

  Suberin, a polyester polymer in the cell wall of terrestrial plants, controls the transport of water and nutrients and protects plant from pathogenic infections and environmental stresses. Structurally, suberin consists of aliphatic and aromatic domains; p -hydroxycinnamates, such as ferulate, p -coumarate, and/or sinapate, are the major phenolic constituents of the latter. By analyzing the “wall-bound” phenolics of mutant lines of Arabidopsis deficient in a family of acyl-CoA dependent acyltransferase (BAHD) genes, we discovered that the formation of aromatic suberin in Arabidopsis , primarily in seed and root tissues, depends on a member of the BAHD superfamily of enzymes encoded by At5g41040 . This enzyme exhibits an ω-hydroxyacid hydroxycinnamoyltransferase activity with an in vitro kinetic preference for feruloyl-CoA and 16-hydroxypalmitic acid. Knocking down or knocking out the At5g41040 gene in Arabidopsis reduces specifically the quantity of ferulate in suberin, but does not affect the accumulation of p -coumarate or sinapate. The loss of the suberin phenolic differentially affects the aliphatic monomer loads and alters the permeability and sensitivity of seeds and roots to salt stress. This highlights the importance of suberin aromatics in the polymer's function.

  陆地植物细胞壁中的聚酯聚合物亚脂素控制着水分和营养物质的运输，并保护植物免受病原体感染和环境压力的影响。在结构上，亚脂素由脂肪族和芳香族结构域组成；香豆酸、香豆素和/或芥子酸等

  -羟基肉桂酸是后者的主要酚类成分。通过分析缺乏一类酰辅酶A依赖性酰转移酶（BAHD）基因的突变株的“壁结合”酚类物质，我们发现芥菜中芳香族亚脂素的形成，主要在种子和根组织中，取决于由At5g41040编码的BAHD超家族酶的成员。该酶表现出ω-羟基酸羟基肉桂酰转移酶活性，对于香草酰辅酶A和16-羟基棕榈酸具有体外动力学偏好。在芥菜中敲除或沉默At5g41040基因，会特异性减少亚脂素中香豆酸的含量，但不会影响香豆素或芥子酸的积累。亚脂素酚类的丧失不同程度地影响脂肪族单体的负载，并改变种子和根对盐胁迫的渗透性和敏感性。这突显了亚脂素芳香族在聚合物功能中的重要性。
• Expression and Characterization of CYP4V2 as a Fatty Acid ω-Hydroxylase
  作者：Mariko Nakano、Edward J. Kelly、Allan E. Rettie

  DOI：10.1124/dmd.109.028530

  日期：2009.11

  Bietti's crystalline dystrophy is an ocular disease that is strongly associated with polymorphisms in the CYP4V2 gene. CYP4 enzymes are typically microsomal fatty acid ω-hydroxylases that function together with mitochondrial and peroxisomal β-oxidation enzymes to degrade cellular lipids. Indeed, ocular and peripheral cells cultured from patients with Bietti's have been reported to exhibit abnormal lipid metabolism. However, CYP4V2 possesses low sequence homology to other members of the CYP4 family. Therefore, we cloned and expressed CYP4V2 and analyzed the functional characteristics of this new cytochrome P450 enzyme. We find that CYP4V2 is a selective ω-hydroxylase of saturated, medium-chain fatty acids with relatively high catalytic efficiency toward myristic acid. Moreover, N -hydroxy- N ′-(4- n -butyl-2-methylphenyl formamidine) (HET0016) is a nanomolar inhibitor of the enzyme. Therefore, CYP4V2 exhibits catalytic functions typical of a human CYP4 enzyme, but with a distinctive chain-length selectivity coupled with high ω-hydroxylase specificity. Consequently, defective ω-oxidation of ocular fatty acids/lipids secondary to mutations in the CYP4V2 gene appears to be a plausible mechanism underlying Bietti's crystalline dystrophy.

  比蒂晶体营养不良症是一种眼部疾病，与 CYP4V2 基因的多态性密切相关。CYP4 酶是典型的微粒体脂肪酸ω-羟化酶，与线粒体和过氧化物酶β-氧化酶共同作用，降解细胞脂质。事实上，有报道称，从 Bietti's 症患者身上培养出的眼部和外周细胞表现出异常的脂质代谢。然而，CYP4V2 与 CYP4 家族其他成员的序列同源性较低。因此，我们克隆并表达了 CYP4V2，并分析了这种新细胞色素 P450 酶的功能特征。我们发现，CYP4V2 是饱和中链脂肪酸的选择性ω-羟化酶，对肉豆蔻酸的催化效率相对较高。此外，N-羟基-N ′-（4-正丁基-2-甲基苯基甲脒）（HET0016）是该酶的纳摩尔抑制剂。因此，CYP4V2 具有人类 CYP4 酶的典型催化功能，但具有独特的链长选择性和高ω-羟化酶特异性。因此，CYP4V2 基因突变导致的眼脂肪酸/脂质的ω-氧化缺陷似乎是导致比蒂晶体营养不良症的一个合理机制。
• CYP704B1 Is a Long-Chain Fatty Acid <i>ω</i>-Hydroxylase Essential for Sporopollenin Synthesis in Pollen of Arabidopsis    
  作者：Anna A. Dobritsa、Jay Shrestha、Marc Morant、Franck Pinot、Michiyo Matsuno、Robert Swanson、Birger Lindberg Møller、Daphne Preuss

  DOI：10.1104/pp.109.144469

  日期：2009.10.1

  Sporopollenin is the major component of the outer pollen wall (exine). Fatty acid derivatives and phenolics are thought to be its monomeric building blocks, but the precise structure, biosynthetic route, and genetics of sporopollenin are poorly understood. Based on a phenotypic mutant screen in Arabidopsis (Arabidopsis thaliana), we identified a cytochrome P450, designated CYP704B1, as being essential for exine development. CYP704B1 is expressed in the developing anthers. Mutations in CYP704B1 result in impaired pollen walls that lack a normal exine layer and exhibit a characteristic striped surface, termed zebra phenotype. Heterologous expression of CYP704B1 in yeast cells demonstrated that it catalyzes ω-hydroxylation of long-chain fatty acids, implicating these molecules in sporopollenin synthesis. Recently, an anther-specific cytochrome P450, denoted CYP703A2, that catalyzes in-chain hydroxylation of lauric acid was also shown to be involved in sporopollenin synthesis. This shows that different classes of hydroxylated fatty acids serve as essential compounds for sporopollenin formation. The genetic relationships between CYP704B1, CYP703A2, and another exine gene, MALE STERILITY2, which encodes a fatty acyl reductase, were explored. Mutations in all three genes resulted in pollen with remarkably similar zebra phenotypes, distinct from those of other known exine mutants. The double and triple mutant combinations did not result in the appearance of novel phenotypes or enhancement of single mutant phenotypes. This implies that each of the three genes is required to provide an indispensable subset of fatty acid-derived components within the sporopollenin biosynthesis framework.

  孢粉素是花粉外壁（外壳）的主要成分。脂肪酸衍生物和酚类被认为是其单体组成部分，但孢粉素的精确结构、生物合成途径和遗传学仍不清楚。通过在拟南芥（拟南芥）中进行表型突变筛选，我们确定了一种细胞色素P450，称为CYP704B1，作为外壳发育的关键因素。CYP704B1在发育的花药中表达。CYP704B1的突变导致花粉壁受损，缺乏正常的外壳层，并表现出特征性的条纹表面，称为斑马表型。在酵母细胞中异源表达CYP704B1表明，它催化长链脂肪酸的ω-羟化，暗示这些分子参与了孢粉素的合成。最近，一种花药特异性的细胞色素P450，称为CYP703A2，被证明参与孢粉素的合成，它催化月桂酸的链内羟化。这表明，不同类别的羟化脂肪酸作为孢粉素形成的必需化合物。探讨了CYP704B1、CYP703A2和另一种外壳基因MALE STERILITY2之间的遗传关系，后者编码脂肪酰还原酶。所有三种基因的突变导致花粉呈现出非常相似的斑马表型，与其他已知的外壳突变体不同。双重和三重突变组合并没有出现新的表型或增强单一突变体表型。这意味着每个基因都需要在孢粉素生物合成框架中提供必不可少的脂肪酸衍生组分。

• Expression and Characterization of <i>CYP52</i> Genes Involved in the Biosynthesis of Sophorolipid and Alkane Metabolism from Starmerella bombicola
  作者：Fong-Chin Huang、Alyssa Peter、Wilfried Schwab

  DOI：10.1128/aem.02886-13

  日期：2014.1.15

  Three cytochrome P450 monooxygenase CYP52 gene family members were isolated from the sophorolipid-producing yeast Starmerella bombicola (former Candida bombicola ), namely, CYP52E3 , CYP52M1 , and CYP52N1 , and their open reading frames were cloned into the pYES2 vector for expression in Saccharomyces cerevisiae . The functions of the recombinant proteins were analyzed with a variety of alkane and fatty acid substrates using microsome proteins or a whole-cell system. CYP52M1 was found to oxidize C ₁₆ to C ₂₀ fatty acids preferentially. It converted oleic acid (C _18:1 ) more efficiently than stearic acid (C _18:0 ) and linoleic acid (C _18:2 ) and much more effectively than α-linolenic acid (C _18:3 ). No products were detected when C ₁₀ to C ₁₂ fatty acids were used as the substrates. Moreover, CYP52M1 hydroxylated fatty acids at their ω- and ω-1 positions. CYP52N1 oxidized C ₁₄ to C ₂₀ saturated and unsaturated fatty acids and preferentially oxidized palmitic acid, oleic acid, and linoleic acid. It only catalyzed ω-hydroxylation of fatty acids. Minor ω-hydroxylation activity against myristic acid, palmitic acid, palmitoleic acid, and oleic acid was shown for CYP52E3. Furthermore, the three P450s were coassayed with glucosyltransferase UGTA1. UGTA1 glycosylated all hydroxyl fatty acids generated by CYP52E3, CYP52M1, and CYP52N1. The transformation efficiency of fatty acids into glucolipids by CYP52M1/UGTA1 was much higher than those by CYP52N1/UGTA1 and CYP52E3/UGTA1. Taken together, CYP52M1 is demonstrated to be involved in the biosynthesis of sophorolipid, whereas CYP52E3 and CYP52N1 might be involved in alkane metabolism in S. bombicola but downstream of the initial oxidation steps.

  摘要 三种细胞色素 P450 单加氧酶 CYP52 基因家族成员从产槐脂酵母 酵母 前 念珠菌 )中分离出CYP52基因家族成员，即 CYP52E3 , CYP52M1 和 CYP52N1 及其开放阅读框克隆到 pYES2 载体中，以便在 酵母中表达。 .使用微粒体蛋白或全细胞系统分析了重组蛋白在多种烷烃和脂肪酸底物中的功能。研究发现 CYP52M1 可氧化 C 16 氧化为 C 20 脂肪酸。它将油酸（C 18:1 ）比硬脂酸（C 18:0 ）和亚油酸（C 18:2 比硬脂酸（C 18:0 ）和亚油酸（C 18:2 ）更有效，比 α-亚麻酸（C 18:3 ).当 C 10 至 C 12 脂肪酸作为底物时，未检测到产物。此外，CYP52M1 对脂肪酸的 ω- 和 ω-1 位进行羟化。CYP52N1 氧化 C 14 氧化为 C 20 饱和及不饱和脂肪酸，并优先氧化棕榈酸、油酸和亚油酸。它只催化脂肪酸的ω-羟基化。CYP52E3 对肉豆蔻酸、棕榈酸、棕榈油酸和油酸的ω-羟化活性较小。此外，还对这三种 P450 与葡萄糖基转移酶 UGTA1 进行了共同测定。UGTA1 对 CYP52E3、CYP52M1 和 CYP52N1 产生的所有羟基脂肪酸进行糖基化。CYP52M1/UGTA1 将脂肪酸转化为糖脂的效率远远高于 CYP52N1/UGTA1 和 CYP52E3/UGTA1。综上所述，CYP52M1 被证明参与了槐脂的生物合成，而 CYP52E3 和 CYP52N1 则可能参与了烷烃的代谢。 S. bombicola 但处于初始氧化步骤的下游。