4-Oxobutanoate

• 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: 4-Oxobutanoate
• 化学式: C4H5O3-
• 分子量: 101.08
• InChiKey: UIUJIQZEACWQSV-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  7
• 可旋转键数：
  2
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  57.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  水 、 NADP⁺ 、 4-Oxobutanoate 生成 氢(+1)阳离子 、 NADPH(4-) 、 琥珀酸根
  参考文献：
  名称：

  尼古丁分解代谢的最后步骤。γ-N-甲基氨基丁酸酯的脱氨基与脱甲基

  摘要：

  尼古丁分解代谢的新酶已被鉴定和表征，该酶可用于烟碱节杆菌pAO1对烟草生物碱的解毒作用。尼古丁分解会从羟基吡啶环形成尼古丁蓝，并从分子的吡咯烷环形成γ-N-甲基氨基丁酸酯（CH3-4-氨基丁酸酯）。出乎意料的是，可以确定出CH3-4-氨基丁酸酯分解代谢最终步骤的两种替代途径。最近鉴定的γ-N-甲基氨基丁酸酯氧化酶可能会将CH3-4氨基丁酸酯脱甲基化为γ-N-氨基丁酸酯[Chiribau et al。（2004）Eur J Biochem271，4677-4684]。在另一种途径中，具有非共价结合的FAD的胺氧化酶具有新颖的底物特异性，可从CH3-4-氨基丁酸酯中去除甲胺，形成琥珀酸半醛。琥珀酸半醛通过NADP +依赖性琥珀酸半醛脱氢酶转化为琥珀酸。琥珀酸酯可进入柠檬酸循环，从而完成尼古丁的吡咯烷部分的分解代谢。这些酶的基因表达取决于生长培养基中尼古丁的存在。因此，尼古丁调节剂的两种酶，γ-

  DOI：

  10.1111/j.1742-4658.2006.05173.x
• 作为产物：
  描述：

  4-hydroxy-2-oxo-1,7-heptane-dioate 生成 piruvate 、 4-Oxobutanoate
  参考文献：
  名称：

  丙酮酸特异性II类醛缩酶HpaI的纯化和生化特性。

  摘要：

  HpaI，II类丙酮酸特异性醛缩酶，与羟苯乙酸的分解代谢途径有关，被过表达和纯化。基于HpaI的生化研究并未证实基于同源2-dehydro-3-deoxygalactarate醛缩酶的晶体结构，磷酸盐参与丙酮酸的质子转移。因此，在HEPES钠缓冲液和Tris-乙酸盐缓冲液中，酶对底物4-羟基-2-酮戊酸的比活度高于磷酸钠缓冲液。该酶还催化无丙酮缓冲液中丙酮酸质​​子交换的部分反应，初始速率为0.77 mmol min（-）（1）mg（-）（1），通过核磁共振监测。稳态动力学分析表明，该酶还能够催化4-羟基-2-酮己酸和3-脱氧-d-甘露糖-辛基-2-核糖酸（KDO）的羟醛裂解。该酶显示出明显的草酰乙酸脱羧酶活性，其ak（cat）值比4-羟基-2-酮戊酸的羟醛裂解的相应值高2.4倍。草酸钠是酶催化反应的烯醇中间体的类似物，是该酶的竞争性抑制剂，K（i）值为5.5 microM。通过位点特异性

  DOI：

  10.1021/bi050607y

文献信息

• Novel 4-(8X-6,11-dihydrodibenzo-[b.e.]-thiepin-11-one-3-yl)-4-oxobutyric
  申请人：Syntex (U.S.A.) Inc.

  公开号：US04130654A1

  公开（公告）日：1978-12-19

  This invention relates to novel 4-(8X-6,11-dihydrodibenzo-[b.e.]-thiepin-11-one-3-yl)-4-oxobutyric acids and their derivatives, wherein X is hydrogen, methoxy or chloro, methods of preparation, compositions and uses thereof.

  本发明涉及新型的4-(8X-6,11-二氢二苯并[b.e.]噻吩-11-酮-3-基)-4-氧代丁酸及其衍生物，其中X为氢、甲氧基或氯，其制备方法、组合物及其用途。
• Final steps in the catabolism of nicotine. Deamination versus demethylation of gamma-N-methylaminobutyrate
  作者：Calin-Bogdan Chiribau、Marius Mihasan、Petra Ganas、Gabor L. Igloi、Vlad Artenie、Roderich Brandsch

  DOI：10.1111/j.1742-4658.2006.05173.x

  日期：2006.4

  NADP+‐dependent succinic semialdehyde dehydrogenase. Succinate may enter the citric acid cycle completing the catabolism of the pyrrolidine moiety of nicotine. Expression of the genes of these enzymes was dependent on the presence of nicotine in the growth medium. Thus, two enzymes of the nicotine regulon, γ‐N‐methylaminobutyrate oxidase and amine oxidase share the same substrate. The Km of 2.5 mm and

  尼古丁分解代谢的新酶已被鉴定和表征，该酶可用于烟碱节杆菌pAO1对烟草生物碱的解毒作用。尼古丁分解会从羟基吡啶环形成尼古丁蓝，并从分子的吡咯烷环形成γ-N-甲基氨基丁酸酯（CH3-4-氨基丁酸酯）。出乎意料的是，可以确定出CH3-4-氨基丁酸酯分解代谢最终步骤的两种替代途径。最近鉴定的γ-N-甲基氨基丁酸酯氧化酶可能会将CH3-4氨基丁酸酯脱甲基化为γ-N-氨基丁酸酯[Chiribau et al。（2004）Eur J Biochem271，4677-4684]。在另一种途径中，具有非共价结合的FAD的胺氧化酶具有新颖的底物特异性，可从CH3-4-氨基丁酸酯中去除甲胺，形成琥珀酸半醛。琥珀酸半醛通过NADP +依赖性琥珀酸半醛脱氢酶转化为琥珀酸。琥珀酸酯可进入柠檬酸循环，从而完成尼古丁的吡咯烷部分的分解代谢。这些酶的基因表达取决于生长培养基中尼古丁的存在。因此，尼古丁调节剂的两种酶，γ-
• Computational Prediction and Experimental Verification of the Gene Encoding the NAD⁺/NADP⁺-Dependent Succinate Semialdehyde Dehydrogenase in<i>Escherichia coli</i>
  作者：Tobias Fuhrer、Lifeng Chen、Uwe Sauer、Dennis Vitkup

  DOI：10.1128/jb.01027-07

  日期：2007.11.15

  Although NAD⁺-dependent succinate semialdehyde dehydrogenase activity was first described inEscherichia colimore than 25 years ago, the responsible gene has remained elusive so far. As an experimental proof of concept for a gap-filling algorithm for metabolic networks developed earlier, we demonstrate here that theE. coligeneyneIis responsible for this activity. Our biochemical results demonstrate that theyneI-encoded succinate semialdehyde dehydrogenase can use either NAD⁺or NADP⁺to oxidize succinate semialdehyde to succinate. The gene is induced by succinate semialdehyde, and expression data indicate thatyneIplays a unique physiological role in the general nitrogen metabolism ofE. coli. In particular, we demonstrate using mutant growth experiments that theyneIgene has an important, but not essential, role during growth on arginine and probably has an essential function during growth on putrescine as the nitrogen source. The NADP⁺-dependent succinate semialdehyde dehydrogenase activity encoded by the functional homologgabDappears to be important for nitrogen metabolism under N limitation conditions. TheyneI-encoded activity, in contrast, functions primarily as a valve to prevent toxic accumulation of succinate semialdehyde. Analysis of available genome sequences demonstrated that orthologs of bothyneIandgabDare broadly distributed across phylogenetic space.

  摘要虽然 25 年多以前就在大肠埃希菌（Escherichia colimia）中首次描述了依赖 NAD+ 的琥珀酸半醛脱氢酶活性，但至今仍未找到负责的基因。作为早先开发的代谢网络填隙算法的实验性概念证明，我们在这里证明了大肠埃希菌neI负责这一活性。我们的生化结果表明，它们编码的琥珀酸半醛脱氢酶可以使用 NAD+ 或 NADP+ 将琥珀酸半醛氧化成琥珀酸。该基因由琥珀酸半醛诱导，表达数据表明 yneI 在大肠杆菌的一般氮代谢中发挥着独特的生理作用。特别是，我们利用突变体生长实验证明，yneI 基因在以精氨酸为氮源的生长过程中起着重要作用，但并非必不可少，而在以腐胺为氮源的生长过程中可能起着至关重要的作用。在氮限制条件下，功能同源物 gabD 所编码的依赖 NADP+ 的琥珀酸半醛脱氢酶活性对氮代谢非常重要。与此相反，他们的编码活性主要起阀门作用，防止琥珀酸半醛的毒性积累。对现有基因组序列的分析表明，bothyneI和gabD的直向同源物广泛分布于系统发育空间。
• Molecular analysis of two genes of the Escherichia coli gab cluster: nucleotide sequence of the glutamate:succinic semialdehyde transaminase gene (gabT) and characterization of the succinic semialdehyde dehydrogenase gene (gabD)
  作者：K Bartsch、A von Johnn-Marteville、A Schulz

  DOI：10.1128/jb.172.12.7035-7042.1990

  日期：1990.12

  We have characterized two genes of the Escherichia coli K-12 gab cluster, which encodes the enzymes of the 4-aminobutyrate degradation pathway. The nucleotide sequence of gabT, coding for glutamate:succinic semialdehyde transaminase (EC 2.6.1.19), alternatively known as 4-aminobutyrate transaminase, was determined. The structural gene consists of 1,281 nucleotides specifying a protein of 426 amino acids with a molecular mass of 45.76 kDa. The protein shows significant homologies to the ornithine transaminases from Saccharomyces cerevisiae and from rat and human mitochondria. Three functionally and structurally important amino acid residues of the transaminase were identified by sequence comparison studies, and evolutionary relationships of the aminotransferases are discussed. The gabD gene, encoding succinic semialdehyde dehydrogenase (EC 1.2.1.16), was cloned and shown to be located adjacent to the 5' end of gabT. Expression studies with subfragments of the initially cloned DNA region revealed a maximal size of 1.7 kb for gabD. Both genes are cotranscribed from a promoter located upstream of gabD.

  我们已经表征了大肠杆菌K-12 gab簇的两个基因，该簇编码4-氨基丁酸降解途径的酶。确定了gabT的核苷酸序列，编码谷氨酸：琥珀酸半醛转氨酶（EC 2.6.1.19），又称4-氨基丁酸转氨酶。该结构基因由1,281个核苷酸组成，指定了一个由426个氨基酸组成、分子量为45.76 kDa的蛋白质。该蛋白质与酵母和大鼠、人类线粒体的鸟氨酸转氨酶显示出显著的同源性。通过序列比较研究，确定了转氨酶的三个功能和结构上重要的氨基酸残基，并讨论了氨基转移酶的进化关系。克隆了编码琥珀酸半醛脱氢酶（EC 1.2.1.16）的gabD基因，并显示其位于gabT的5'端相邻。利用最初克隆的DNA区域的亚片段进行表达研究，发现gabD的最大大小为1.7 kb。两个基因都是从位于gabD上游的启动子共同转录的。
• Plant Succinic Semialdehyde Dehydrogenase. Cloning, Purification, Localization in Mitochondria, and Regulation by Adenine Nucleotides
  作者：Karin B. Busch、Hillel Fromm

  DOI：10.1104/pp.121.2.589

  日期：1999.10.1

  Succinic semialdehyde dehydrogenase (SSADH) is one of three enzymes constituting the γ-aminobutyric acid shunt. We have cloned the cDNA for SSADH from Arabidopsis, which we designated SSADH1. SSADH1 cDNA encodes a protein of 528 amino acids (56 kD) with high similarity to SSADH fromEscherichia coli and human (&gt;59% identity). A sequence similar to a mitochondrial protease cleavage site is present 33 amino acids from the N terminus, indicating that the mature mitochondrial protein may contain 495 amino acids (53 kD). The native recombinant enzyme and the plant mitochondrial protein have a tetrameric molecular mass of 197 kD. Fractionation of plant mitochondria revealed its localization in the matrix. The purified recombinant enzyme showed maximal activity at pH 9.0 to 9.5, was specific for succinic semialdehyde (K  0.5 = 15 μm), and exclusively used NAD+ as a cofactor (K  m = 130 ± 77 μm). NADH was a competitive inhibitor with respect to NAD+(K  i = 122 ± 86 μm). AMP, ADP, and ATP inhibited the activity of SSADH (K  i = 2.5–8 mm). The mechanism of inhibition was competitive for AMP, noncompetitive for ATP, and mixed competitive for ADP with respect to NAD+. Plant SSADH may be responsive to mitochondrial energy charge and reducing potential in controlling metabolism of γ-aminobutyric acid.

  琥珀酸半醛脱氢酶（SSADH）是构成γ-氨基丁酸途径的三种酶之一。我们从拟南芥中克隆了SSADH的cDNA，将其命名为SSADH1。SSADH1 cDNA编码一个528个氨基酸（56 kD）的蛋白质，与大肠杆菌和人类的SSADH具有高度相似性（&gt;59％的同源性）。距离N末端33个氨基酸处存在类似于线粒体蛋白酶剪切位点的序列，表明成熟的线粒体蛋白可能包含495个氨基酸（53 kD）。天然重组酶和植物线粒体蛋白的四聚体分子量为197 kD。植物线粒体的分离表明其定位在基质中。纯化的重组酶在pH 9.0至9.5时显示最大活性，对琥珀酸半醛具有特异性（K 0.5 = 15 μm），并且仅使用NAD +作为辅因子（K m = 130 ± 77 μm）。 NADH是相对于NAD +的竞争性抑制剂（K i = 122 ± 86 μm）。 AMP，ADP和ATP抑制SSADH的活性（K i = 2.5-8 mm）。抑制机制对于AMP是竞争性的，对于ATP是非竞争性的，对于ADP相对于NAD +是混合竞争性的。植物SSADH可能对线粒体能量和还原潜力敏感，从而控制γ-氨基丁酸的代谢。