Tyramin

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: Tyramin
• 英文别名: 4-Hydroxy-β-phenaethyl-ammonium；4-(2-amino-ethyl)-phenol; protonated form；tyramine cation；[4-(2-Aminoethyl)phenyl]oxidanium；[4-(2-aminoethyl)phenyl]oxidanium
• 化学式: C₈H₁₁NO*H
• 分子量: 138.189
• InChiKey: DZGWFCGJZKJUFP-UHFFFAOYSA-O

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  10
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  47.9
• 氢给体数：
  2
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  氧气 、 Tyramin 生成 dopamine
  参考文献：
  名称：

  来自冈比亚按蚊的前酚氧化酶（PPO）的结构提供了对PPO激活机制的新见解。

  摘要：

  背景技术酚氧化酶（PO）催化的黑色素化是昆虫针对病原性和寄生虫感染的普遍防御机制。在诸如冈比亚按蚊（Anopheles gambiae）之类的蚊子中，黑色素囊化作用是对某些引起疟疾和丝虫病的寄生虫的抵抗机制。PO最初是由血细胞合成的，并以无活性的酚氧化酶（PPO）的形式释放到血淋巴中，在识别外来入侵者时被丝氨酸蛋白酶级联激活。PPO活化和PO催化的机理一直难以捉摸。结果在此，我们报道了来自冈比亚按蚊的PPO8的晶体结构，分辨率为2.6。PPO8形成同型二聚体，每个亚基均显示出经典的III型双铜活性中心。我们的分子对接和诱变研究揭示了一个新的底物结合位点，其中Glu364作为负责单酚和双酚底物去质子化的催化残基。Glu364的突变严重损害了AgPPO8的单酚羟化酶和双酚氧化酶的活性。我们的数据表明，新发现的底物结合口袋是催化的实际位点，并且可以实现PPO活化而无需撤出之前被视为底物“占位符”

  DOI：

  10.1186/s12915-015-0225-2
• 作为产物：
  描述：

  氢(+1)阳离子 、 L-酪氨酸 生成 二氧化碳 、 Tyramin
  参考文献：
  名称：

  Identification of theEnterococcus faecalisTyrosine Decarboxylase Operon Involved in Tyramine Production

  摘要：

  摘要通过筛选粪肠球菌插入突变体文库，分离出了一个影响酪胺产生的突变体。该突变体在麦氏肉汤中的生长情况与野生型粪肠球菌JH2-2菌株相似，而高效液相色谱分析显示，野生型菌株高达1,000 μg ml-1的酪胺产量被完全取消。对插入基因座的遗传分析表明，该基因编码的脱羧酶与真核生物的酪氨酸脱羧酶相似。序列分析发现了一个磷酸吡哆醛结合位点，表明这种酶属于使用这种辅助因子的氨基酸脱羧酶家族。反转录-PCR分析表明，粪肠球菌JH2-2的假定酪氨酸脱羧酶编码基因（tdc）与下游的假定酪氨酸-酪氨酸反转录酶编码基因和上游的酪氨酸-tRNA合成酶基因共转录。这项研究首次描述了原核生物中的酪氨酸脱羧酶基因。

  DOI：

  10.1128/aem.68.7.3537-3544.2002

文献信息

• Rice histone deacetylase 10 and Arabidopsis histone deacetylase 14 genes encode <i>N</i> -acetylserotonin deacetylase, which catalyzes conversion of <i>N</i> -acetylserotonin into serotonin, a reverse reaction for melatonin biosynthesis in plants
  作者：Kyungjin Lee、Hyoung Yool Lee、Kyoungwhan Back

  DOI：10.1111/jpi.12460

  日期：2018.3

  screened 4 genes that were known as histone deacetylase (HDAC) genes, but encoded proteins targeted into chloroplasts or mitochondria rather than nuclei. Of 4 recombinant Escherichia coli strains expressing these genes, one E. coli strain expressing the rice HDAC10 gene was found to be capable of producing serotonin in response to treatment with NAS. The recombinant purified rice HDAC10 (OsHDAC10)

  在植物中，褪黑激素的产生受到严格的调节，这与其褪色素的前体的产生不同，后者是对衰老和病原体暴露等刺激产生高度诱导作用的。外源性5-羟色胺处理不会在植物中极大地诱导N-乙酰5-羟色胺（NAS）和褪黑激素的产生，这表明从5-羟色胺生物合成褪黑激素的途径中可能存在一个或多个调控基因。在此报告中，我们发现NAS在水稻幼苗中迅速大量转化为5-羟色胺，表明存在N-乙酰5-羟色胺脱乙酰基酶（ASDAC）。为了克隆假定的ASDAC基因，我们筛选了4个被称为组蛋白脱乙酰基酶（HDAC）的基因。）基因，但编码的蛋白质靶向叶绿体或线粒体而不是细胞核。在表达这些基因的4种重组大肠杆菌菌株中，发现一种表达水稻HDAC10基因的大肠杆菌菌株能够响应于NAS处理而产生5-羟色胺。重组纯化的水稻HDAC10（OsHDAC10）蛋白对NAS，N-乙酰酪胺（NAT），N具有ASDAC酶活性-乙酰色胺和褪黑激素，对于NAT具有
• [EN] MEANS FOR USE IN PREPARATION OF HYDROGEL BASED ON HYDROXYPHENYL DERIVATIVE OF HYALURONAN, METHOD OF HYDROGEL PREPARATION AND USE THEREOF<br/>[FR] MOYEN DESTINÉ À ÊTRE UTILISÉ DANS UNE PRÉPARATION D'HYDROGEL À BASE DE DÉRIVÉ HYDROXYPHÉNYLE D'HYALURONANE, PROCÉDÉ DE PRÉPARATION D'HYDROGEL ET UTILISATION ASSOCIÉE
  申请人：CONTIPRO AS

  公开号：WO2020249143A1

  公开（公告）日：2020-12-17

  Means for use in a preparation of a hydrogel that comprises two separate solutions A and B, of which the solution A comprises enzyme horseradish peroxidase and the solution B comprises hydrogen peroxide, at least one solution A or B comprising calcium ions in form of a pharmaceutically acceptable salt and further the solution A and/or the solution B comprises hydroxyphenyl derivative of hyaluronan of a general formula (I), wherein n is in the range of 2 to 7500 and R is OH or a substituent NHR2CONHR1ArOH of a general formula (II), wherein Ar is phenylene and R1 ethylene or Ar is indolylene and R1 is ethylene or Ar is hydroxyphenylene and R1 is carboxyethylene, and R2 is alkylene of number of carbon atoms 3 to 7. The present invention further relates to the hydrogel based on hydroxyphenyl derivative of hyaluronan and the method of preparation and use thereof.

  用于制备羟基凝胶的方法，包括两种单独的溶液A和B，其中溶液A包括酶辣根过氧化物酶，溶液B包括过氧化氢，至少一种溶液A或B包括以药用可接受盐的形式的钙离子，而且溶液A和/或溶液B包括羟基苯基透明质酸衍生物，其一般式为(I)，其中n在2到7500的范围内，R为OH或一种一般式(II)的取代基NHR2CONHR1ArOH，其中Ar为苯基，R1为乙烯或Ar为吲哚基，R1为乙烯或Ar为羟基苯基，R1为羧基乙烯，R2为碳原子数为3到7的烷基。本发明还涉及基于羟基苯基透明质酸衍生物的羟基凝胶，以及其制备和使用方法。
• Functional Analysis of the Amine Substrate Specificity Domain of Pepper Tyramine and Serotonin <i>N</i>-Hydroxycinnamoyltransferases
  作者：Sei Kang、Kiyoon Kang、Gap Chae Chung、Doil Choi、Atsushi Ishihara、Dong-Sun Lee、Kyoungwhan Back

  DOI：10.1104/pp.105.071514

  日期：2006.2.1

  Pepper (Capsicum annuum) serotonin N-hydroxycinnamoyltransferase (SHT) catalyzes the synthesis of N-hydroxycinnamic acid amides of serotonin, including feruloylserotonin and p-coumaroylserotonin. To elucidate the domain or the key amino acid that determines the amine substrate specificity, we isolated a tyramine N-hydroxycinnamoyltransferase (THT) gene from pepper. Purified recombinant THT protein catalyzed the synthesis of N-hydroxycinnamic acid amides of tyramine, including feruloyltyramine and p-coumaroyltyramine, but did not accept serotonin as a substrate. Both the SHT and THT mRNAs were found to be expressed constitutively in all pepper organs. Pepper SHT and THT, which have primary sequences that are 78% identical, were used as models to investigate the structural determinants responsible for their distinct substrate specificities and other enzymatic properties. A series of chimeric genes was constructed by reciprocal exchange of DNA segments between the SHT and THT cDNAs. Functional characterization of the recombinant chimeric proteins revealed that the amino acid residues 129 to 165 of SHT and the corresponding residues 125 to 160 in THT are critical structural determinants for amine substrate specificity. Several amino acids are strongly implicated in the determination of amine substrate specificity, in which glycine-158 is involved in catalysis and amine substrate binding and tyrosine-149 plays a pivotal role in controlling amine substrate specificity between serotonin and tyramine in SHT. Furthermore, the indisputable role of tyrosine is corroborated by the THT-F145Y mutant that uses serotonin as the acyl acceptor. The results from the chimeras and the kinetic measurements will direct the creation of additional novel N-hydroxycinnamoyltransferases from the various N-hydroxycinnamoyltransferases found in nature.

  辣椒（Capsicum annuum）血清素N-羟基肉桂酰转移酶（SHT）催化合成血清素的N-羟基肉桂酰胺，包括香草酰血清素和对香豆酰血清素。为了阐明决定胺基底物特异性的区域或关键氨基酸，我们从辣椒中分离出一种酪胺N-羟基肉桂酰转移酶（THT）基因。纯化的重组THT蛋白催化合成酪胺的N-羟基肉桂酰胺，包括香草酰酪胺和对香豆酰酪胺，但不接受血清素作为底物。辣椒器官中均有SHT和THT mRNA的表达。利用主要序列相似度为78%的辣椒SHT和THT作为模型，研究了决定它们不同底物特异性和其他酶性质的结构因素。通过SHT和THT cDNA之间DNA片段的互换构建了一系列嵌合基因。重组嵌合蛋白的功能特性表明，SHT的129至165个氨基酸残基和THT中相应的125至160个残基是胺基底物特异性的关键结构因素。几个氨基酸强烈涉及胺基底物特异性的确定，其中甘氨酸-158参与催化和胺基底物结合，酪氨酸-149在SHT中在控制血清素和酪胺之间的胺基底物特异性方面起着关键作用。此外，酪氨酸的不可争议作用得到了THT-F145Y突变体的证实，该突变体使用血清素作为酰基受体。嵌合体和动力学测量的结果将指导从自然界中发现的各种N-羟基肉桂酰转移酶中创建额外的新型N-羟基肉桂酰转移酶。

• Crystal structure of tyrosine decarboxylase and identification of key residues involved in conformational swing and substrate binding
  作者：Haixia Zhu、Guochao Xu、Kai Zhang、Xudong Kong、Ruizhi Han、Jiahai Zhou、Ye Ni

  DOI：10.1038/srep27779

  日期：——

  Tyrosine decarboxylase (TDC) is a pyridoxal 5-phosphate (PLP)-dependent enzyme and is mainly responsible for the synthesis of tyramine, an important biogenic amine. In this study, the crystal structures of the apo and holo forms of Lactobacillus brevis TDC (LbTDC) were determined. The LbTDC displays only 25% sequence identity with the only reported TDC structure. Site-directed mutagenesis of the conformationally flexible sites and catalytic center was performed to investigate the potential catalytic mechanism. It was found that H241 in the active site plays an important role in PLP binding because it has different conformations in the apo and holo structures of LbTDC. After binding to PLP, H241 rotated to the position adjacent to the PLP pyridine ring. Alanine scanning mutagenesis revealed several crucial regions that determine the substrate specificity and catalytic activity. Among the mutants, the S586A variant displayed increased catalytic efficiency and substrate affinity, which is attributed to decreased steric hindrance and increased hydrophobicity, as verified by the saturation mutagenesis at S586. Our results provide structural information about the residues important for the protein engineering of TDC to improve catalytic efficiency in the green manufacturing of tyramine.

  摘要：酪氨酸脱羧酶（TDC）是一种依赖于吡哆醛5-磷酸（PLP）的酶，主要负责合成重要的生物胺类物质酪胺。本研究确定了Lactobacillus brevis TDC（LbTDC）的裸形式和全形式的晶体结构。LbTDC与唯一报道的TDC结构仅具有25％的序列同源性。通过构象灵活的位点和催化中心的定向突变来研究其潜在的催化机制。发现活性位点中的H241在PLP结合中起着重要作用，因为在LbTDC的裸形式和全形式中具有不同的构象。在与PLP结合后，H241旋转到邻近PLP吡啶环的位置。丙氨酸扫描突变揭示了几个关键区域，决定底物特异性和催化活性。在突变体中，S586A变异体显示出提高的催化效率和底物亲和力，这归因于空间位阻的减少和亲疏性的增加，通过S586的饱和突变得到验证。我们的结果提供了有关蛋白质工程中重要残基的结构信息，以提高TDC在酪胺的绿色制造中的催化效率。
• Gut bacterial tyrosine decarboxylases restrict levels of levodopa in the treatment of Parkinson’s disease
  作者：Sebastiaan P. van Kessel、Alexandra K. Frye、Ahmed O. El-Gendy、Maria Castejon、Ali Keshavarzian、Gertjan van Dijk、Sahar El Aidy

  DOI：10.1038/s41467-019-08294-y

  日期：——

  Human gut microbiota senses its environment and responds by releasing metabolites, some of which are key regulators of human health and disease. In this study, we characterize gut-associated bacteria in their ability to decarboxylate levodopa to dopamine via tyrosine decarboxylases. Bacterial tyrosine decarboxylases efficiently convert levodopa to dopamine, even in the presence of tyrosine, a competitive substrate, or inhibitors of human decarboxylase. In situ levels of levodopa are compromised by high abundance of gut bacterial tyrosine decarboxylase in patients with Parkinson’s disease. Finally, the higher relative abundance of bacterial tyrosine decarboxylases at the site of levodopa absorption, proximal small intestine, had a significant impact on levels of levodopa in the plasma of rats. Our results highlight the role of microbial metabolism in drug availability, and specifically, that abundance of bacterial tyrosine decarboxylase in the proximal small intestine can explain the increased dosage regimen of levodopa treatment in Parkinson’s disease patients.

  人类肠道微生物群感知其环境并通过释放代谢产物做出反应，其中一些代谢产物是人类健康和疾病的关键调节因子。在本研究中，我们表征了与肠道相关的细菌在通过酪氨酸脱羧酶将左旋多巴转化为多巴胺方面的能力。细菌酪氨酸脱羧酶能够高效地将左旋多巴转化为多巴胺，即使存在竞争性底物酪氨酸或人类脱羧酶的抑制剂。在帕金森病患者中，肠道细菌酪氨酸脱羧酶的高丰度影响了左旋多巴的原位水平。最后，吸收左旋多巴的部位——近端小肠中细菌酪氨酸脱羧酶的相对丰度对大鼠血浆中左旋多巴的水平有显著影响。我们的研究结果强调了微生物代谢在药物可用性中的作用，特别是近端小肠中细菌酪氨酸脱羧酶的丰度可以解释帕金森病患者中左旋多巴治疗的剂量增加。