L-gulonate | 2002-49-5

• 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: L-gulonate
• 英文别名: (2S,3S,4R,5S)-2,3,4,5,6-pentahydroxyhexanoate
• CAS: 2002-49-5
• 化学式: C₆H₁₁O₇
• 分子量: 195.149
• InChiKey: RGHNJXZEOKUKBD-QTBDOELSSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  -2.7
• 重原子数：
  13
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  141
• 氢给体数：
  5
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  tetrahydroxo borate 、 L-gulonate 以 重水 为溶剂， 生成
  参考文献：
  名称：

  Duin, M. van; Peters, J. A.; Kieboom, A. P. G., Recueil des Travaux Chimiques des Pays-Bas, 1986, vol. 105, p. 488 - 493

  摘要：

  DOI：
• 作为产物：
  描述：

  水 、 L-古洛糖酸-gamma-内酯 生成 氢(+1)阳离子 、 L-gulonate
  参考文献：
  名称：

  衰老标记蛋白30在L-抗坏血酸的生物合成中起葡萄糖酸内酰胺酶的作用，其敲除小鼠容易坏血病。

  摘要：

  我们最初将衰老标记蛋白30（SMP30）鉴定为一种独特的蛋白，其表达会随着衰老而以雄激素非依赖性方式降低。在这里，我们报告通过使用blast搜索在两种细菌葡萄糖酸内酰胺酶（GNLs）中发现的序列同源性。然后，通过生化研究，我们确定SMP30为动物物种的内酯水解酶GNL。从大鼠肝脏中纯化得到的SMP30对各种醛糖内酯具有内酯酶活性，例如d-和l-葡萄糖酸-δ-内酯，d-和l-古洛诺-γ-内酯以及d-和l-半乳糖-γ-内酯，其中Zn（2+）或Mn（2+）作为辅助因子的要求。此外，在SMP30基因敲除小鼠中，肝脏中未检测到GNL活性。因此，我们得出结论，SMP30是肝脏中唯一的GNL。与l-古洛糖醇-γ-内酯的内酯酶反应是l-抗坏血酸（AA）生物合成中的倒数第二个步骤，在这里通过使用SMP30基因敲除小鼠的营养研究证实了SMP30在该合成过程中的重要作用。这些喂养维生素C缺乏饮食的基因剔除小鼠（n

  DOI：

  10.1073/pnas.0511225103

文献信息

• Myo-inositol oxygenases
  申请人：——

  公开号：US20040185562A1

  公开（公告）日：2004-09-23

  The invention provides methods and materials related to the production of organic products such as glucuronic acid, ascorbic acid, and glucaric acid. Specifically, the invention provides cells, methods for culturing cells, isolated nucleic acid molecules, and methods and materials for producing various organic products such as glucuronic acid, ascorbic acid, and glucaric acid.

  该发明提供了与有机产品（如葡萄糖醛酸，抗坏血酸和葡萄糖酸）生产相关的方法和材料。具体地，该发明提供了细胞、细胞培养方法、分离核酸分子以及生产各种有机产品（如葡萄糖醛酸、抗坏血酸和葡萄糖酸）的方法和材料。
• Prediction of enzymatic pathways by integrative pathway mapping
  作者：Sara Calhoun、Magdalena Korczynska、Daniel J Wichelecki、Brian San Francisco、Suwen Zhao、Dmitry A Rodionov、Matthew W Vetting、Nawar F Al-Obaidi、Henry Lin、Matthew J O'Meara、David A Scott、John H Morris、Daniel Russel、Steven C Almo、Andrei L Osterman、John A Gerlt、Matthew P Jacobson、Brian K Shoichet、Andrej Sali

  DOI：10.7554/elife.31097

  日期：——

  The functions of most proteins are yet to be determined. The function of an enzyme is often defined by its interacting partners, including its substrate and product, and its role in larger metabolic networks. Here, we describe a computational method that predicts the functions of orphan enzymes by organizing them into a linear metabolic pathway. Given candidate enzyme and metabolite pathway members, this aim is achieved by finding those pathways that satisfy structural and network restraints implied by varied input information, including that from virtual screening, chemoinformatics, genomic context analysis, and ligand -binding experiments. We demonstrate this integrative pathway mapping method by predicting the L-gulonate catabolic pathway in Haemophilus influenzae Rd KW20. The prediction was subsequently validated experimentally by enzymology, crystallography, and metabolomics. Integrative pathway mapping by satisfaction of structural and network restraints is extensible to molecular networks in general and thus formally bridges the gap between structural biology and systems biology.

  大多数蛋白质的功能尚未确定。酶的功能通常由其相互作用的伙伴（包括其底物和产物）及其在更大的代谢网络中的作用来定义。在此，我们介绍一种计算方法，通过将孤儿酶组织到线性代谢途径中来预测其功能。在给定候选酶和代谢物通路成员的情况下，通过寻找满足各种输入信息（包括来自虚拟筛选、化学信息学、基因组上下文分析和配体结合实验的信息）所隐含的结构和网络限制的通路来实现这一目标。我们通过预测流感嗜血杆菌 Rd KW20 中的 L-古洛糖酸分解途径，展示了这种综合途径图绘制方法。随后，我们通过酶学、晶体学和代谢组学实验对预测结果进行了验证。通过满足结构和网络约束条件来绘制整合通路图的方法可扩展到一般的分子网络，从而在结构生物学和系统生物学之间架起了一座正式的桥梁。
• Structural and Functional Characterization of Rabbit and Human l-Gulonate 3-Dehydrogenase
  作者：S. Ishikura

  DOI：10.1093/jb/mvi033

  日期：2005.3.1

  l-Gulonate 3-dehydrogenase (GDH) catalyzes the NAD+-linked dehydrogenation of l-gulonate into dehydro-l-gulonate in the uronate cycle. In this study, we isolated the enzyme and its cDNA from rabbit liver, and found that the cDNA is identical to that for rabbit lens λ-crystallin except for lacking a codon for Glu309. The same cDNA species, but not the λ-crystallin cDNA with the codon for Glu309, was detected in the lens, which showed the highest GDH activity among rabbit tissues. In addition, recombinant human λ-crystallin that lacks Glu309 displays enzymatic properties similar to rabbit GDH. These data indicate that GDH is recruited as λ-crystallin without gene duplication. An outstanding feature of GDH is modulation of its activity by low concentrations of Pi, which decreases the catalytic efficiency in a dose dependent manner. Pi also protects the enzyme against both thermal and urea denaturation. Kinetic analysis suggests that Pi binds to both the free enzyme and its NAD(H)-complex in the sequential ordered mechanism. Furthermore, we examined the roles of Asp36, Ser124, His145, Glu157 and Asn196 in the catalytic function of rabbit GDH by site-directed mutagenesis. The D36R mutation leads to a switch in favor of NADP(H) specificity, suggesting an important role of Asp36 in the coenzyme specificity. The S124A mutation decreases the catalytic efficiency 500-fold, and the H145Q, N196Q and N195D mutations result in inactive enzyme forms, although the E157Q mutation produces no large kinetic alteration. Thus, Ser124, His145 and Asn196 may be critical for the catalytic function of GDH.

  l-gulonate 3-脱氢酶（GDH）在尿酸循环中催化与 NAD+ 链接的 l-gulonate 脱氢为脱氢-l-gulonate。在这项研究中，我们从兔肝脏中分离出了这种酶及其 cDNA，并发现除了缺少 Glu309 的密码子外，该 cDNA 与兔晶状体 λ-结晶素的 cDNA 完全相同。在兔组织中 GDH 活性最高的晶状体中检测到了相同的 cDNA，但没有检测到带有 Glu309 密码子的 λ-结晶素 cDNA。此外，缺乏 Glu309 的重组人 λ-结晶素显示出与兔 GDH 相似的酶特性。这些数据表明，GDH 与 λ-结晶素一样是在没有基因复制的情况下被招募的。GDH 的一个突出特点是其活性受低浓度 Pi 的调节，Pi 会以剂量依赖的方式降低催化效率。Pi 还能保护酶免受热变性和尿素变性的影响。动力学分析表明，Pi 与游离酶及其 NAD（H）-复合物的结合是有序的。此外，我们还通过定点突变研究了 Asp36、Ser124、His145、Glu157 和 Asn196 在兔 GDH 催化功能中的作用。D36R 突变导致了 NADP（H）特异性的转换，表明 Asp36 在辅酶特异性中起着重要作用。S124A 突变使催化效率降低了 500 倍，H145Q、N196Q 和 N195D 突变导致酶处于非活性状态，但 E157Q 突变没有产生大的动力学改变。因此，Ser124、His145 和 Asn196 可能对 GDH 的催化功能至关重要。
• The pathway for L-gulonate catabolism in<i>Escherichia coli</i>K-12 and<i>Salmonella typhimurium</i>LT-2
  作者：Ronald A. Cooper

  DOI：10.1016/0014-5793(80)80727-7

  日期：1980.6.16

  3-phosphate and pyruvate [3], L-Gulonate is the 3-epimer of L-galactonate and if its catabolic were analogous to that of L-galactonate it would be converted into fructuronate and thus enter the route for bacterial glucuronate degradation thereby yielding glyceraldehyde 3-phosphate and pyruvate (fig.1). On the other hand the only reported route for L-gulonate catabolism is as part of the ~ucuronate degra~tion

  细菌中葡萄糖醛酸的分解代谢途径与动物不同，细菌中的葡萄糖醛酸通过依次形成果糖醛酸、甘露糖酸、2-oxo-3 转化为~y~er~dehyde 3-磷酸和丙酮酸。 deoxygluconate 和 2-oxo-3-deoxygluconate 6.phosphate [ 11. 在动物中，葡萄糖醛酸通过 L*-古洛糖酸、3-氧-L-古洛糖酸、L-木酮糖、木糖醇和木酮糖的连续形成被分解代谢为 5-磷酸木酮糖[2]。在大肠杆菌中，L-半乳糖酸 Kl 2 被分解代谢为甘油醛 3-磷酸和丙酮酸 [3]，L-古洛糖酸是 L-半乳糖酸的 3-差向异构体，如果其分解代谢与 L-半乳糖酸类似，它将被转化转化为果糖醛酸，从而进入细菌葡萄糖醛酸降解的途径，从而产生 3-磷酸甘油醛和丙酮酸（图 1）。另一方面，唯一报道的 L-古洛糖酸分解代谢途径是动物的~糖醛酸降解序列的一部分，导致形成 5-磷酸木酮糖。我们已经观察到各种肠道细菌可以在
• In vivo role of aldehyde reductase
  作者：Motoko Takahashi、Satoshi Miyata、Junichi Fujii、Yoko Inai、Shigemitsu Ueyama、Motoko Araki、Tomoyoshi Soga、Reiko Fujinawa、Chiaki Nishitani、Shigeru Ariki、Takeyuki Shimizu、Tomomi Abe、Yoshito Ihara、Morimitsu Nishikimi、Yasunori Kozutsumi、Naoyuki Taniguchi、Yoshio Kuroki

  DOI：10.1016/j.bbagen.2012.07.003

  日期：2012.11

  Background: Aldehyde reductase (AKR1A; EC 1.1.1.2) catalyzes the reduction of various types of aldehydes. To ascertain the physiological role of AKR1A, we examined AKR1A knockout mice.Methods: Ascorbic acid concentrations in AKR1A knockout mice tissues were examined, and the effects of human AKR1A transgene were analyzed. We purified AKR1A and studied the activities of glucuronate reductase and glucuronolactone reductase, which are involved in ascorbic acid biosynthesis. Metabolomic analysis and DNA microarray analysis were performed for a comprehensive study of AKR1A knockout mice.Results: The levels of ascorbic acid in tissues of AKR1A knockout mice were significantly decreased which were completely restored by human AKR1A transgene. The activities of glucuronate reductase and glucuronolactone reductase, which are involved in ascorbic acid biosynthesis, were suppressed in AKR1A knockout mice. The accumulation of D-glucuronic acid and saccharate in knockout mice tissue and the expression of acute-phase proteins such as serum amyloid A2 are significantly increased in knockout mice liver.Conclusions: AKR1A plays a predominant role in the reduction of both D-glucuronic acid and D-glucurono-gamma-lactone in vivo. The knockout of AKR1A in mice results in accumulation of D-glucuronic acid and saccharate as well as a deficiency of ascorbic acid, and also leads to upregulation of acute phase proteins.General significance: AKR1A is a major enzyme that catalyzes the reduction of D-glucuronic acid and D-glucurono-gamma-lactone in vivo, besides acting as an aldehyde-detoxification enzyme. Suppression of AKR1A by inhibitors, which are used to prevent diabetic complications, may lead to the accumulation of D-glucuronic acid and saccharate. (C) 2012 Elsevier B.V. All rights reserved.