[(2R)-2-hydroxy-2-(4-hydroxyphenyl)ethyl]azanium

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: [(2R)-2-hydroxy-2-(4-hydroxyphenyl)ethyl]azanium
• 化学式: C8H12NO2+
• 分子量: 154.19
• InChiKey: QHGUCRYDKWKLMG-QMMMGPOBSA-O

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  11
• 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：
  68.1
• 氢给体数：
  3
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  [(2R)-2-hydroxy-2-(4-hydroxyphenyl)ethyl]azanium 生成 4-羟基苯乙醛 、 铵
  参考文献：
  名称：

  Initial catabolism of aromatic biogenic amines by Pseudomonas aeruginosa PAO: pathway description, mapping of mutations, and cloning of essential genes

  摘要：

  假单胞菌PAO1能够利用多种芳香族生物胺作为唯一的碳源或氮源。其中包括苯乙胺、多巴胺和苯基乙醇胺。苯乙胺的初始降解是通过膜结合的苯乙胺脱氢酶介导的，该酶以苯乙胺为底物产生4-羟基苯乙醛（4HPAL）。该酶在两类胺的生长条件下均被诱导。八胺的初始降解（除非八胺作为唯一的碳源和氮源存在）是通过可溶性酶介导的，该酶对苯基乙醇胺具有活性，但对苯乙胺或多巴胺没有活性。以八胺为底物的反应产物也是4HPAL。在反应混合物中加入NAD可产生4-羟基苯乙酸和NADH。这些活性，八胺水解酶和4-HPAL脱氢酶（作为一个联合活性测量，OCAH-4HPALDH），仅在生长于苯基乙醇胺的条件下被诱导。然而，在以八胺作为唯一的碳源和氮源生长的细胞提取物中未观察到这些联合活性，这表明在这种生长条件下使用了另一种途径。两个独立分离的突变株无法利用苯乙胺作为唯一的碳源或氮源。这些突变株也无法利用多巴胺，但在苯基乙醇胺上以野生型速率生长。这些突变位点位于PAO1染色体上的约70分钟处，与染色体移动质粒R68.45相关联，并且两者与catA1、mtu-9002、tyu-9009和puuE突变相关。克隆了能够补充这两种突变的DNA，其长度约为13.8千碱基对的单个BamHI片段。对亚克隆片段的分析表明这两种突变位于不同的基因中。

  DOI：

  10.1128/jb.169.6.2398-2404.1987
• 作为产物：
  描述：

  抗坏血酸 、 氧气 、 Tyramin 生成 [(2R)-2-hydroxy-2-(4-hydroxyphenyl)ethyl]azanium 、 水 、 L-dehydroascorbate
  参考文献：
  名称：

  域间远程电子转移成为酪胺 β-单加氧酶 Y216A 变体的限速器

  摘要：

  酪胺 β-单加氧酶 (TβM) 属于具有重要生理意义的单核二铜单加氧酶的小型真核家族。该家族的特性包括相距约 11 埃的非耦合单核铜中心，Cu M执行 C–H 和 O 2活化，Cu H用作电子存储位点 [Klinman, JP (2006) J. Biol. 化学 281 , 3013–3016]。保守的酪氨酸（Y216在TβM）定位在所述铜域之间，并且与相关联的Cu ħ通过与铜的相互作用（ħ-协调组氨酸）。Y216 处的突变（对 W、I 和 A）表明电子顺磁共振光谱差异很小或没有差异，而 X 射线吸收光谱研究表明，还原酶中Cu M与其 Met471 配体之间的距离只有很小的减少。高效液相色谱分析表明，Y216W 和 Y216I 完成底物的周转，而 Y216A 经历二次失活，这与 Cu M 上的配体氧化有关。研究了稳态动力学和同位素效应测量。Y216A显着升高的K m,Tyr，以及非常大的D

  DOI：

  10.1021/bi3013609

文献信息

• Initial catabolism of aromatic biogenic amines by Pseudomonas aeruginosa PAO: pathway description, mapping of mutations, and cloning of essential genes
  作者：S M Cuskey、V Peccoraro、R H Olsen

  DOI：10.1128/jb.169.6.2398-2404.1987

  日期：1987.6

  Pseudomonas aeruginosa PAO1 was able to utilize several aromatic biogenic amines as sole sources of carbon or nitrogen. These included the phenethylamines tyramine and dopamine and the phenethanolamines octopamine, synephrine, and norepinephrine. Initial catabolism of the phenethylamines was mediated by a membrane-bound tyramine dehydrogenase which produced 4-hydroxyphenylacetaldehyde (4HPAL) with tyramine as the substrate. The enzyme was induced by growth with both classes of amines. Initial catabolism of octopamine (except when present as the sole source of carbon and nitrogen) was mediated by a soluble enzyme with activity against the phenethanolamines but not against tyramine or dopamine. The product of the reaction with octopamine as substrate was also 4HPAL. Addition of NAD to reaction mixtures yielded 4-hydroxyphenylacetic acid and NADH. These activities, octopamine hydrolyase and 4-HPAL dehydrogenase (measured as a combined activity, OCAH-4HPALDH), were only induced by growth with phenethanolamines. However, the combined activities were not observed in extracts from cells grown with octopamine as the sole source of carbon and nitrogen, suggesting that an alternate pathway is used under this growth condition. Two independently isolated mutant strains were unable to utilize tyramine as a sole source of carbon or nitrogen. These mutants were also unable to utilize dopamine but grew at wild-type rates on the phenethanolamines. The mutations were mapped at about 70 min on the PAO1 chromosome with the chromosome-mobilizing plasmid R68.45, and both were linked to the catA1, mtu-9002, tyu-9009, and puuE mutations. DNA complementing both of the mutations was cloned on a single BamHI fragment approximately 13.8 kilobase pairs in length. Analysis of a subcloned fragment showed that the two mutations were in different genes.

  假单胞菌PAO1能够利用多种芳香族生物胺作为唯一的碳源或氮源。其中包括苯乙胺、多巴胺和苯基乙醇胺。苯乙胺的初始降解是通过膜结合的苯乙胺脱氢酶介导的，该酶以苯乙胺为底物产生4-羟基苯乙醛（4HPAL）。该酶在两类胺的生长条件下均被诱导。八胺的初始降解（除非八胺作为唯一的碳源和氮源存在）是通过可溶性酶介导的，该酶对苯基乙醇胺具有活性，但对苯乙胺或多巴胺没有活性。以八胺为底物的反应产物也是4HPAL。在反应混合物中加入NAD可产生4-羟基苯乙酸和NADH。这些活性，八胺水解酶和4-HPAL脱氢酶（作为一个联合活性测量，OCAH-4HPALDH），仅在生长于苯基乙醇胺的条件下被诱导。然而，在以八胺作为唯一的碳源和氮源生长的细胞提取物中未观察到这些联合活性，这表明在这种生长条件下使用了另一种途径。两个独立分离的突变株无法利用苯乙胺作为唯一的碳源或氮源。这些突变株也无法利用多巴胺，但在苯基乙醇胺上以野生型速率生长。这些突变位点位于PAO1染色体上的约70分钟处，与染色体移动质粒R68.45相关联，并且两者与catA1、mtu-9002、tyu-9009和puuE突变相关。克隆了能够补充这两种突变的DNA，其长度约为13.8千碱基对的单个BamHI片段。对亚克隆片段的分析表明这两种突变位于不同的基因中。
• Characterization of<b><i>Drosophila Tyramine β-Hydroxylase</i></b>Gene and Isolation of Mutant Flies Lacking Octopamine
  作者：Maria Monastirioti、Charles E. Linn, Jr.、Kalpana White

  DOI：10.1523/jneurosci.16-12-03900.1996

  日期：1996.6.15

  Octopamine is likely to be an important neuroactive molecule in invertebrates. Here we report the molecular cloning of theDrosophila melanogastergene, which encodes tyramine β-hydroxylase (TBH), the enzyme that catalyzes the last step in octopamine biosynthesis. The deduced amino acid sequence of the encoded protein exhibits 39% identity to the evolutionarily related mammalian dopamine β-hydroxylase enzyme. We generated a polyclonal antibody against the protein product ofTβhgene, and we demonstrate that the TBH expression pattern is remarkably similar to the previously described octopamine immunoreactivity inDrosophila. We further report the creation of null mutations at theTβhlocus, which result in complete absence of TBH protein and blockage of the octopamine biosynthesis.Tβh-null flies are octopamine-less but survive to adulthood. They are normal in external morphology, but the females are sterile, because although they mate, they retain fully developed eggs. Finally, we demonstrate that this defect in egg laying is associated with the octopamine deficit, because females that have retained eggs initiate egg laying when transferred onto octopamine-supplemented food.

  多巴胺可能是无脊椎动物体内一种重要的神经活性分子。我们在此报告了黑腹果蝇基因的分子克隆，该基因编码酪胺β-羟化酶（TBH），它是催化章胺生物合成最后一步的酶。编码蛋白的氨基酸序列推导结果显示，它与哺乳动物进化相关的多巴胺β-羟化酶有39%的相同性。我们生成了针对Tβh基因蛋白产物的多克隆抗体，并证明TBH的表达模式与之前描述的果蝇中的章胺免疫反应非常相似。我们进一步报告了在Tβhlocus上产生的无效突变，这些突变导致TBH蛋白完全缺失，并阻断了章鱼胺的生物合成。它们的外部形态正常，但雌性不育，因为它们虽然交配，但仍保留发育完全的卵。最后，我们证明了这种产卵缺陷与缺乏章鱼胺有关，因为保留卵的雌蝇在转移到补充章鱼胺的食物上时开始产卵。
• Inactivation of Met471Cys Tyramine β-Monooxygenase Results from Site-Specific Cysteic Acid Formation
  作者：Robert L. Osborne、Hui Zhu、Anthony T. Iavarone、Corinna R. Hess、Judith P. Klinman

  DOI：10.1021/bi300456f

  日期：2012.9.25

  Tyramine beta-monooxygenase (T beta M), the insect homologue of dopamine beta-monooxygenase, is a neuro-regulatory enzyme that catalyzes the beta-hydroxylation of tyramine to yield octopamine. Mutation of the methionine (Met) ligand to Cu-M of T beta M, Met471Cys, yielded a form of T beta M that is catalytically active but susceptible to inactivation during turnover [Hess, C. R., Wu, Z., Ng, A, Gray, E. E., McGuirl, M. M., and Klinman, J. P. (2008) J. Am. Chem. Soc. 130, 11939-11944]. Further, although the wild-type (WT) enzyme undergoes coordination of Met471 to Cum in its reduced form, the generation of Met471Cys almost completely eliminates this interaction [Hess, C. R., Klinman, J. P., and Blackburn, N. J. (2010) J, Biol. Inorg. Chem. 15, 1195-1207]. The aim of this study is to identify the chemical consequence of the poor ability of Cys to coordinate Cum. We show that Met471Cys T beta M is similar to 5-fold more susceptible to inactivation than the WT enzyme in the presence of the cosubstrate/reductant ascorbate and that this process is not facilitated by the substrate tyramine. The resulting 50-fold smaller ratio for turnover to inactivation in the case of Met471Cys prevents full turnover of the substrate under all conditions examined. Liquid chromatography-tandem mass spectrometry analysis of proteolytic digests of inactivated Met471Cys T beta M leads to the identification of cysteic acid at position 471. While both Met and Cys side chains are expected to be similarly subject to oxidative damage in proteins, the enhanced reactivity of Met471Cys toward solution oxidants in T beta M is attributed to its weaker interaction with Cu(I)(M).
• Physiological functions and pharmacological and toxicological effects of<i>p</i>-octopamine
  作者：Sidney J. Stohs

  DOI：10.3109/01480545.2014.900069

  日期：2015.1.2

  p-Octopamine occurs naturally in plants, invertebrates and animals with diverse functions and effects. This review summarizes the chemistry, metabolism, receptor binding characteristics, known physiological functions, and pharmacological and toxicological effects of p-octopamine. Databases used included PubMed and Google Scholar Advanced. p-Octopamine binds to neuroreceptors in insects that are not present in humans, while exhibiting poor binding to alpha-1, alpha-2, beta-1, and beta-2 adrenergic receptors in mammalian systems. p-Octopamine modestly binds to beta-3 adrenergic receptors and may therefore promote lipolysis and weight loss. p-Octopamine is produced in brain and nerve tissues of mammals and is present and can be measured in the blood of normal human subjects. p-Octopamine is considered to be a CNS stimulant in spite of the fact that it binds poorly to adrenergic receptors. Variations occur in blood levels in association with neurological and hepatic diseases. Its precise role in normal neurophysiology is unclear. No human studies have been reported that demonstrate adverse cardiovascular effects following oral administration. No human studies have examined the effects of p-octopamine on athletic performance or weight loss and weight management. A need exists for both animal and human safety and efficacy studies involving oral administration of p-octopamine.
• Interdomain Long-Range Electron Transfer Becomes Rate-Limiting in the Y216A Variant of Tyramine β-Monooxygenase
  作者：Robert L. Osborne、Hui Zhu、Anthony T. Iavarone、Ninian J. Blackburn、Judith P. Klinman

  DOI：10.1021/bi3013609

  日期：2013.2.19

  The enzyme tyramine β-monooxygenase (TβM) belongs to a small eukaryotic family of physiologically important mononuclear dicopper monooxygenases. The properties of this family include noncoupled mononuclear copper centers ∼11 Å apart, with CuM performing C–H and O2 activation and CuH functioning as an electron storage site [Klinman, J. P. (2006) J. Biol. Chem. 281, 3013–3016]. A conserved tyrosine (Y216

  酪胺 β-单加氧酶 (TβM) 属于具有重要生理意义的单核二铜单加氧酶的小型真核家族。该家族的特性包括相距约 11 埃的非耦合单核铜中心，Cu M执行 C–H 和 O 2活化，Cu H用作电子存储位点 [Klinman, JP (2006) J. Biol. 化学 281 , 3013–3016]。保守的酪氨酸（Y216在TβM）定位在所述铜域之间，并且与相关联的Cu ħ通过与铜的相互作用（ħ-协调组氨酸）。Y216 处的突变（对 W、I 和 A）表明电子顺磁共振光谱差异很小或没有差异，而 X 射线吸收光谱研究表明，还原酶中Cu M与其 Met471 配体之间的距离只有很小的减少。高效液相色谱分析表明，Y216W 和 Y216I 完成底物的周转，而 Y216A 经历二次失活，这与 Cu M 上的配体氧化有关。研究了稳态动力学和同位素效应测量。Y216A显着升高的K m,Tyr，以及非常大的D