malic semialdehyde

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羟基酸及其衍生物
• 英文名称: malic semialdehyde
• 英文别名: (3R)-3-hydroxy-4-oxobutanoate
• 化学式: C₄H₅O₄
• 分子量: 117.081
• InChiKey: QWHDXIUUXWGQME-GSVOUGTGSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  -0.7
• 重原子数：
  8
• 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：
  77.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  左旋肉碱 在 氧气 、 carnitine oxygenase from Acinetobacter baumannii 、 carnitine reductase from Acinetobacter baumannii 、 还原型辅酶Ⅰ 作用下， 生成 malic semialdehyde 、 三甲胺
  参考文献：
  名称：

  人类微生物群中的Rieske型加氧酶的光活化电子转移和肉碱氧化的催化机理

  摘要：

  含非血红素铁的鲍曼不动杆菌（Ab）加氧酶CntA /还原酶CntB对季铵底物肉碱的氧化作用与人类心血管疾病的发作有关。本文中，我们开发了NADH的蓝光（365 nm）激活以及电子顺磁共振（EPR）测量，以研究电子从NADH激发态到氧化的Rieske型[2Fe-2S] 2+团簇的转移在具有和不具有底物肉碱的AbCntA加氧酶结构域中。单电子进一步减少的电子转移，Rieske型[2Fe-2S] 1+通过桥接的谷氨酸盐E205将AbCntA-WT的中心转移到单核非血红素铁中心，随后的催化作用仅在肉碱存在下发生。AbCntA-E205A突变体中的电子转移过程受到严重影响，这可能解释了AbCntA-E205A突变体中催化活性的重大损失。NADH光活化与EPR结合可广泛用于在低温下捕获反应性中间体，并创造了一种表征多种含氧化还原中心的蛋白质中难以捉摸的中间体的新方法。

  DOI：

  10.1002/anie.202012381

文献信息

• Structural basis of carnitine monooxygenase CntA substrate specificity, inhibition, and intersubunit electron transfer
  作者：Mussa Quareshy、Muralidharan Shanmugam、Eleanor Townsend、Eleanor Jameson、Timothy D.H. Bugg、Alexander D. Cameron、Yin Chen

  DOI：10.1074/jbc.ra120.016019

  日期：2021.1

  the same monomer but adjacent in two neighbouring monomers. Structural determination of CntA and subsequent electron paramagnetic resonance measurements uncover the molecular basis of the so-called bridging glutamate (E205) residue in inter-subunit electron transfer. The structures of the substrate-bound CntA help to define the substrate pocket. Importantly, a tyrosine residue (Y203) is essential for

  肉碱在肠道中的微生物代谢为三甲胺（TMA）可以加速动脉粥样硬化和心脏病，因此这些产生TMA的酶是重要的药物靶标。在这里，我们报告肉碱加氧酶CntA的第一个结构，该酶是Rieske加氧酶家族的一种酶。CntA以头尾a3三聚体结构存在。两个功能性结构域（Rieske和催化性单核铁结构域）在同一单体中的位置> 40Å，但在两个相邻的单体中的位置相邻。CntA的结构确定和随后的电子顺磁共振测量揭示了亚单位间电子转移中所谓的桥接谷氨酸（E205）残基的分子基础。底物结合的CntA的结构有助于限定底物袋。重要的，酪氨酸残基（Y203）对于通过与季铵基团的π阳离子相互作用进行配体识别至关重要。芳香族残基和季胺底物之间的这种相互作用使我们能够从参与环境中芳香族污染物生物修复的原型环羟基化Rieske加氧酶中描绘出Rieske加氧酶的亚组（V组）。此外，我们报告了第一个已知的CntA抑制剂的发现，并解决了与
• Carnitine metabolism in the human gut: characterization of the two-component carnitine monooxygenase CntAB from Acinetobacter baumannii
  作者：Marco Massmig、Edward Reijerse、Joern Krausze、Christoph Laurich、Wolfgang Lubitz、Dieter Jahn、Jürgen Moser

  DOI：10.1074/jbc.ra120.014266

  日期：2020.9

  approaches. Protein ligands of the flavin mononucleotide (FMN) and the plant-type [2Fe-2S] cluster of CntB and also of the Rieske-type [2Fe-2S] cluster and the mononuclear [Fe] center of CntA were identified. EPR spectroscopy of variant CntA proteins suggested a hierarchical metallocenter maturation, Rieske [2Fe-2S] followed by the mononuclear [Fe] center. NADH-dependent electron transfer via the redox

  肠道微生物群中肉碱细菌形成的三甲胺 (TMA) 与心血管疾病有关。在此过程中，双组分肉碱单加氧酶 (CntAB) 催化肉碱依赖氧裂解为 TMA 和苹果酸半醛。基于诱变和电子顺磁共振 (EPR) 光谱方法研究了还原酶 CntB 和催化组分 CntA 的各个氧化还原状态。鉴定了黄素单核苷酸 (FMN) 和 CntB 的植物型 [2Fe-2S] 簇以及 Rieske 型 [2Fe-2S] 簇和 CntA 的单核 [Fe] 中心的蛋白质配体。变异 CntA 蛋白的 EPR 光谱表明分层金属中心成熟，Rieske [2Fe-2S] 紧随其后的是单核 [Fe] 中心。研究了通过 CntB 的氧化还原成分和在三聚体 CntA 复合物中激活分子氧的 NADH 依赖性电子转移。EPR 实验表明，来自 NADH 的两个电子以黄素半醌自由基的形式分配给植物型 [2Fe-2S] 簇和 FMN。这种还原的 CntB
• Carnitine metabolism to trimethylamine by an unusual Rieske-type oxygenase from human microbiota
  作者：Yijun Zhu、Eleanor Jameson、Marialuisa Crosatti、Hendrik Schäfer、Kumar Rajakumar、Timothy D. H. Bugg、Yin Chen

  DOI：10.1073/pnas.1316569111

  日期：2014.3.18

  Metabolism of l -carnitine, a compound abundant in human diet, to trimethylamine by human microbiota has been shown to promote atherosclerosis and subsequent development of heart disease. However, the underpinning molecular and biochemical mechanisms remain unknown. In this study, we reveal that a previously unidentified Rieske-type protein is responsible for carnitine transformation to trimethylamine from human microbiota. Knowledge gained in our study provides the opportunity not only to explore Rieske protein inhibitors in preventing trimethylamine formation in animal studies and clinical trials, but also for its use as a functional genetic marker to better understand human microbiota and their dynamics in our health and disease in future epidemiological studies and dietary interventions.

  已经显示出人类肠道微生物代谢富含在人类饮食中的化合物L-肉碱生成三甲胺，促进动脉粥样硬化和随后的心脏疾病的发展。然而，其基础的分子和生化机制仍然未知。在这项研究中，我们揭示了一种以前未知的Rieske型蛋白质是人类肠道微生物将肉碱转化为三甲胺的原因。我们研究所获得的知识不仅提供了探索Rieske蛋白质抑制剂以预防动物研究和临床试验中的三甲胺形成的机会，而且还为将其用作功能性基因标记以更好地了解人类肠道微生物及其在我们的健康和疾病中的动态在未来的流行病学研究和饮食干预中提供了机会。

• γ-Butyrobetaine Is a Proatherogenic Intermediate in Gut Microbial Metabolism of L-Carnitine to TMAO
  作者：Robert A. Koeth、Bruce S. Levison、Miranda K. Culley、Jennifer A. Buffa、Zeneng Wang、Jill C. Gregory、Elin Org、Yuping Wu、Lin Li、Jonathan D. Smith、W.H. Wilson Tang、Joseph A. DiDonato、Aldons J. Lusis、Stanley L. Hazen

  DOI：10.1016/j.cmet.2014.10.006

  日期：2014.11

  L-carnitine, a nutrient in red meat, was recently reported to accelerate atherosclerosis via a metaorganismal pathway involving gut microbial trimethylamine (TMA) formation and host hepatic conversion into trimethylamine-N-oxide (TMAO). Herein, we show that following L-carnitine ingestion, gamma-butyrobetaine (gamma BB) is produced as an intermediary metabolite by gut microbes at a site anatomically proximal to and at a rate similar to 1,000-fold higher than the formation of TMA. Moreover, we show that gamma BB is the major gut microbial metabolite formed from dietary L-carnitine in mice, is converted into TMA and TMAO in a gut microbiota-dependent manner (like dietary L-carnitine), and accelerates atherosclerosis. Gut microbial composition and functional metabolic studies reveal that distinct taxa are associated with the production of gamma BB or TMA/TMAO from dietary L-carnitine. Moreover, despite their close structural similarity, chronic dietary exposure to L-carnitine or gamma BB promotes development of functionally distinct microbial communities optimized for the metabolism of L-carnitine or gamma BB, respectively.
• L-carnitine via enzyme-catalyzed oxidative kinetic resolution
  作者：Dennis Ditullio、David Anderson、Ching-Shih Chen、Charles J. Sih

  DOI：10.1016/0968-0896(94)80009-x

  日期：1994.6

  L-Carnitine of high optical purity was prepared via kinetic resolution using a mutant strain of Acinetobacter calcoaceticus ATCC 39647. This organism preferentially metabolized the D-enantiomer of the racemate to furnish L-carnitine. Recovery of L-carnitine was 93%, providing a total weight yield of 46.5% in 92% enantiomeric excess. The mode of degradation of carnitine was shown to proceed via a monooxygenase-catalyzed oxidative cleavage resulting in the formation of trimethylamine and malic acid. The data suggest that the stereoselective metabolism of DL-carnitine is probably the result of differential permeability of the cell membrane towards the optical antipodes.