glutamate γ-semialdehyde | 2886-91-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: glutamate γ-semialdehyde
• 英文别名: L-glutamate-5-semialdehyde；L-glutamic-gamma-semialdehyde；γ-GS；L-glutamate semialdehyde；(S)-2-Amino-5-oxo-valeriansaeure；(S)-2-amino-5-oxo-valeric acid；L-glutamate-γ-semialdehyde；L-2-Amino-4-formyl-buttersaeure；L-GSA；L-Glutaminsaeure-γ-semialdehyd；L-glutamate gamma-semialdehyde；(2S)-2-azaniumyl-5-oxopentanoate
• CAS: 2886-91-1
• 化学式: C₅H₉NO₃
• 分子量: 131.131
• InChiKey: KABXUUFDPUOJMW-BYPYZUCNSA-N

物化性质

• 沸点：
  308.9±37.0 °C(Predicted)
• 密度：
  1.224±0.06 g/cm3(Predicted)
• 物理描述：
  Solid

计算性质

• 辛醇/水分配系数(LogP)：
  -3.8
• 重原子数：
  9
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  80.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  glutamate γ-semialdehyde 、 丙二酰辅酶A-钠盐 在 甲酸 、 carboxymethylproline synthase B from Pectobacterium carotovorum 、 三羟甲基氨基甲烷盐酸盐 作用下， 以 水 为溶剂， 反应 0.17h， 生成 (2S,5S)-trans-5-carboxymethylproline
  参考文献：
  名称：

  Carboxymethylproline synthase catalysed syntheses of functionalised N-heterocycles

  摘要：

  通过从氨基酸醛和（烷基化）丙二酰辅酶 A 衍生物制备功能化的 5、6 和 7 元 N-杂环，证明了野生型和变异型羧甲基脯氨酸合成酶在生物催化方面的用途；生成的 N-杂环通过碳青霉烯合成酶转化为相应的双环 β-内酰胺。

  DOI：

  10.1039/b924519g
• 作为产物：
  描述：

  L-脯氨酸 在 水 、 氧气 、 Thermomicrobium roseum sarcosine oxidase S₃₂₀K/F₂₄₃Y double mutant 作用下， 以 aq. buffer 为溶剂， 反应 72.0h， 生成 glutamate γ-semialdehyde
  参考文献：
  名称：

  重建关键微域的自然进化趋势为热微生物 N-去甲基酶的工程设计提供了有效策略

  摘要：

  据报道， N-去甲基化酶可以去除伯胺或仲胺上的甲基，这可能会进一步影响生物大分子或化合物的性质和功能；然而，尚未系统地研究N-去甲基化酶的底物范围和稳健性。在这里，我们报告了Thermomicrobium roseum肌氨酸氧化酶 (TrSOX) 关键微域中自然进化的再现，这是一种N-脱甲基酶具有显着的稳定性（熔化温度超过 100 °C）和对映选择性，可增强底物范围和对 -CN- 键的催化效率。对于初始框架，我们通过结晶和 X 射线衍射 (XRD) 获得了 TrSOX 的结构。然后使用祖先序列重建 (ASR) 识别关键微结构域的非保守残基（包括催化环、辅酶口袋、底物口袋和入口位点）的自然进化，并通过位点重建自然进化过程中产生的替换。定向诱变。单取代和双取代变体催化N的N-去甲基化-甲基-L-氨基酸分别比野生型快 1800 倍和 6000 倍。此外，这些单取代变体催化了非氨基酸化合物的末端N

  DOI：

  10.1016/j.jbc.2022.101656

文献信息

• Proline biosynthesis in Escherichia coli Stoichiometry and end-product identification of the reaction catalysed by glutamate semialdehyde dehydrogenase
  作者：D J Hayzer、T Leisinger

  DOI：10.1042/bj1970269

  日期：1981.8.1

  The stoichiometry of the oxidative phosphorylation of glutamic acid 5-semialdehyde by gamma-glutamyl phosphate reductase (glutamate semialdehyde dehydrogenase) has been established. Equimolar amounts of NADP+ and L-glutamic acid 5-semialdehyde are consumed and equimolar amounts of 5-oxiopyrroilidine-2-carboxylic acid and NADPH are formed. The end-product of the reaction is demonstrated to be 5-oxopyrrolidine-2-carboxylic acid, probably arising from the true end-product gamma-glutamyl phosphate.

  氧化磷酸化谷氨酸5-半醛的化学计量学已经确定。NADP+和L-谷氨酸5-半醛的量是相等的，消耗掉的量也是相等的，同时生成了5-氧代吡咯啉-2-羧酸和NADPH的等摩尔量。反应的最终产物被证明是5-氧代吡咯啉-2-羧酸，可能来自真正的最终产物γ-谷氨酰磷酸。
• Isolation of the Ornithine-δ-Aminotransferase cDNA and Effect of Salt Stress on Its Expression in <i>Arabidopsis thaliana</i>1
  作者：Nancy H.C.J. Roosens、Tran T. Thu、Hayati M. Iskandar、Michel Jacobs

  DOI：10.1104/pp.117.1.263

  日期：1998.5.1

  To evaluate the relative importance of ornithine (Orn) as a precursor in proline (Pro) synthesis, we isolated and sequenced a cDNA encoding the Orn-δ-aminotransferase (δ-OAT) from Arabidopsis thaliana. The deduced amino acid sequence showed high homology with bacterial, yeast, mammalian, and plant sequences, and the N-terminal residues exhibited several common features with a mitochondrial transit peptide. Our results show that under both salt stress and normal conditions, δ-OAT activity and mRNA in young plantlets are slightly higher than in older plants. This appears to be related to the necessity to dispose of an easy recycling product, glutamate. Analysis of the expression of the gene revealed a close association with salt stress and Pro production. In young plantlets, free Pro content, Δ1-pyrroline-5-carboxylate synthase mRNA, δ-OAT activity, and δ-OAT mRNA were all increased by salt-stress treatment. These results suggest that for A. thaliana, the Orn pathway, together with the glutamate pathway, plays an important role in Pro accumulation during osmotic stress. Conversely, in 4-week-old A. thaliana plants, although free Pro level also increased under salt-stress conditions, the δ-OAT activity appeared to be unchanged and δ-OAT mRNA was not detectable. Δ1-pyrroline-5-carboxylate synthase mRNA was still induced at a similar level. Therefore, for the adult plants the free Pro increase seemed to be due to the activity of the enzymes of the glutamate pathway.

  为了评估鸟氨酸（Orn）作为脯氨酸（Pro）合成的前体的相对重要性，我们从拟南芥中分离并测序了编码Orn-δ-氨基转移酶（δ-OAT）的cDNA。推导出的氨基酸序列与细菌、酵母、哺乳动物和植物序列具有很高的同源性，N-末端残基具有几个与线粒体转运肽的共同特征。我们的结果表明，在盐胁迫和正常条件下，年轻植株中的δ-OAT活性和mRNA略高于老年植株。这似乎与处置易于回收的产物谷氨酸的必要性有关。基因表达分析显示，该基因与盐胁迫和Pro产生密切相关。在年轻植株中，盐胁迫处理后，游离Pro含量、Δ1-吡咯烷酮-5-羧酸合成酶mRNA、δ-OAT活性和δ-OAT mRNA均增加。这些结果表明，在渗透胁迫期间，对于拟南芥而言，Orn途径与谷氨酸途径一起，在Pro积累中发挥重要作用。相反，在4周大的拟南芥植物中，尽管在盐胁迫条件下游离Pro水平也增加了，但δ-OAT活性似乎没有改变，δ-OAT mRNA也无法检测到。 Δ1-吡咯烷酮-5-羧酸合成酶mRNA仍然以相似水平诱导。因此，对于成年植物，游离Pro的增加似乎是由于谷氨酸途径酶的活性。

• Mycobacterium tuberculosis Is a Natural Ornithine Aminotransferase (rocD) Mutant and Depends on Rv2323c for Growth on Arginine
  作者：Annegret Hampel、Claudia Huber、Robert Geffers、Marina Spona-Friedl、Wolfgang Eisenreich、Franz-Christoph Bange

  DOI：10.1371/journal.pone.0136914

  日期：——

  Mycobacterium tuberculosis (Mtb) possesses a genetic repertoire for metabolic pathways, which are specific and fit to its intracellular life style. Under in vitro conditions, Mtb is known to use arginine as a nitrogen source, but the metabolic pathways for arginine utilization have not been identified. Here we show that, in the presence of arginine, Mtb upregulates a gene cluster which includes an ornithine aminotransferase (rocD) and Rv2323c, a gene of unknown function. Isotopologue analysis by using 13C- or 15N-arginine revealed that in Mtb arginine is not only used as nitrogen source but also as carbon source for the formation of amino acids, in particular of proline. Surprisingly, rocD, which is widespread in other bacteria and is part of the classical arginase pathway turned out to be naturally deleted in Mtb, but not in non-tuberculous mycobacteria. Mtb lacking Rv2323c showed a growth defect on arginine, did not produce proline from arginine, and incorporated less nitrogen derived from arginine in its core nitrogen metabolism. We conclude that the highly induced pathway for arginine utilization in Mtb differs from that of other bacteria including non-tuberculous mycobacteria, probably reflecting a specific metabolic feature of intracellular Mtb.

  结核分枝杆菌（Mtb）拥有一套遗传代谢途径，这些途径具有特异性，适合其细胞内的生活方式。在体外条件下，Mtb 可以利用精氨酸作为氮源，但利用精氨酸的代谢途径尚未确定。在这里，我们发现在精氨酸存在的情况下，Mtb 会上调一个基因簇，其中包括一个鸟氨酸氨基转移酶（rocD）和一个功能未知的基因 Rv2323c。利用 13C- 或 15N- 精氨酸进行的同位素分析表明，在 Mtb 中，精氨酸不仅被用作氮源，还被用作形成氨基酸（尤其是脯氨酸）的碳源。令人惊讶的是，在其他细菌中广泛存在的、作为经典精氨酸酶途径一部分的 rocD 在 Mtb 中被自然删除，而在非结核分枝杆菌中却没有。缺乏 Rv2323c 的 Mtb 在精氨酸上表现出生长缺陷，不能从精氨酸中产生脯氨酸，在其核心氮代谢中结合的来自精氨酸的氮较少。我们的结论是，Mtb 利用精氨酸的高诱导途径不同于包括非结核分枝杆菌在内的其他细菌，这可能反映了细胞内 Mtb 的特定代谢特征。
• [delta]1-Pyrroline-5-Carboxylate Dehydrogenase from Cultured Cells of Potato (Purification and Properties)
  作者：G. Forlani、D. Scainelli、E. Nielsen

  DOI：10.1104/pp.113.4.1413

  日期：1997.4.1

  [delta]1-Pyrroline-5-carboxylate (P5C) dehydrogenase (EC 1.5.1.12), the second enzyme in the proline catabolic pathway and a catalyst for the oxidation of P5C to glutamate, was purified from cultured potato (Solanum tuberosum L. var Desiree) cells. Homogeneous enzyme preparations were obtained by a three-step procedure that used anion-exchange, adsorption, and substrate elution chromatography. A 1600-fold purification was achieved, with a recovery of one-third of the initial activity. The purified enzyme was characterized with respect to structural, kinetic, and biochemical properties. It appeared to be an α--4 tetramer with subunits of an apparent molecular mass of about 60 kD and had a mildly acidic isoelectric point value. Potato P5C dehydrogenase had Michaelis constant values of 0.11 and 0.46 mM for NAD+ and P5C, respectively. Although NAD+ was the preferred electron acceptor, NADP+ also yielded an unusually high rate, and thus was found to serve as a substrate. Maximal activity was observed at pH values in the 7.3 to 8.3 range, and was progressively inhibited by chloride ions, a finding that strengthens recent suggestions that hyperosmotic stress negatively modulates in vivo proline oxidation.

  从培养的马铃薯(Solanum tuberosum L. var Desiree)细胞中纯化了[delta]1-吡咯烷酸-5-羧酸脱氢酶(EC 1.5.1.12)，这是脯氨酸降解途径中的第二个酶，催化P5C氧化为谷氨酸。通过离子交换、吸附和底物洗脱层析的三步程序，获得了纯度高的酶制剂。获得了1600倍的纯化，回收了最初活性的三分之一。对纯化酶进行了结构、动力学和生化性质的表征。它似乎是一个α-4四聚体，亚基的表观分子量约为60 kD，并具有轻微酸性的等电点值。马铃薯P5C脱氢酶的米氏常数分别为0.11和0.46 mM，用于NAD+和P5C。虽然NAD+是首选的电子受体，但NADP+也产生了异常高的速率，因此被发现可以作为底物。最大活性在pH值为7.3至8.3的范围内观察到，并且逐渐被氯离子抑制，这一发现加强了最近的建议，即高渗压胁迫负性调节体内脯氨酸氧化。

• Proline Excretion and Indirect Suppression in <i>Escherichia coli</i> and <i>Salmonella typhimurium</i>
  作者：Claire M. Berg、John J. Rossi

  DOI：10.1128/jb.118.3.928-934.1974

  日期：1974.6

  The last step in proline biosynthesis in Escherichia coli K-12, Salmonella typhimurium LT7, and a number of other enterobacterial isolates is regulated so that no proline is excreted, even if excess Δ ¹ -pyrroline-5-carboxylate, the immediate precursor of proline, is added to a culture. In proline auxotrophs blocked at an early step in proline biosynthesis ( proA or proB ), reversion to prototrophy is often due to a mutation in the arginine pathway which diverts N -acetyl glutamate γ-semialdehyde to proline synthesis, thus bypassing the proA or proB block. In such double mutants ( proAB, argD ), the last step in proline synthesis appears to be unregulated, since proline is excreted. Feedback inhibition and repression of the arginine pathway overcomes indirect suppression (restoring the Pro ⁻ phenotype), but proline regulation is not restored; double mutants still excrete proline when fed Δ ¹ -pyrroline-5-carboxylate exogeneously. A new class of proline analogue-resistant mutant, due to mutation at argD , is also described.

  在大肠杆菌K-12、鼠伤寒沙门氏菌LT7和其他一些肠道细菌株中，脯氨酸生物合成的最后一步是被调节的，以便不排出任何脯氨酸，即使向培养基中添加过量的Δ1-吡咯烷酮-5-羧酸，即脯氨酸的直接前体。在脯氨酸辅助营养物在脯氨酸生物合成的早期阻滞（proA或proB）的突变体中，复性往往是由精氨酸途径中的突变引起的，该突变将N-乙酰谷氨酸γ-半醛转向脯氨酸合成，从而绕过proA或proB的阻滞。在这样的双突变体（proAB，argD）中，脯氨酸合成的最后一步似乎是未经调节的，因为脯氨酸被排出。反馈抑制和精氨酸途径的抑制克服了间接抑制（恢复Pro-表型），但脯氨酸调节没有恢复；当给予外源性的Δ1-吡咯烷酮-5-羧酸时，双突变体仍然排出脯氨酸。还描述了一类由于argD突变而产生的脯氨酸类似物耐药突变体。