4-oxo-2-nonenol | 108602-32-0

• 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-oxo-2-nonenol
• 英文别名: 1-Hydroxynon-2-en-4-one；1-hydroxynon-2-en-4-one
• CAS: 108602-32-0
• 化学式: C₉H₁₆O₂
• 分子量: 156.225
• InChiKey: GLYROUYLKGPVGY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  11
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-oxo-2-nonenol 、 N-(2H3)乙酰半胱氨酸 以 乙醇 为溶剂， 反应 2.0h， 生成 ONO-MA-d3
  参考文献：
  名称：

  Quantitation of mercapturic acid conjugates of 4-hydroxy-2-nonenal and 4-oxo-2-nonenal metabolites in a smoking cessation study

  摘要：

  The breakdown of polyunsaturated fatty acids (PUFAs) under conditions of oxidative stress results in the formation of lipid peroxidation (LPO) products. These LPO products such as 4-hydroxy-2-nonenal (HNE) and 4-oxo-2-nonenal (ONE) can contribute to the development of cardiovascular and neurodegenerative diseases and cancer. Conjugation with glutathione, followed by further metabolism to mercapturic acid (MA) conjugates, can mitigate the effects of these LPO products in disease development by facilitating their excretion from the body. We have developed a quantitative method to simultaneously assess levels of 4-oxo-2-nonen-1-ol (ONO)-MA, HNE-MA, and 1,4-dihydroxy-2-nonene (DHN)-MA in human urine samples utilizing isotope-dilution mass spectrometry. We are also able to detect 4-hydroxy-2-nonenoic acid (HNA)MA, 4-hydroxy-2-nonenoic acid lactone (HNAL)-MA, and 4-oxo-2-nonenoic acid (ONA)-MA with this method. The detection of ONO-MA and ONA-MA in humans is significant because it demonstrates that HNE/ONE branching occurs in the breakdown of PUFAs and suggests that ONO may contribute to the harmful effects Currently associated with HNE. We were able to show significant decreases in HNE-MA, DHN-MA, and total LPO-MA in a group of seven smokers upon smoking cessation. These data demonstrate the value of HNE and ONE metabolites as in vivo markers of oxidative stress. (C) 2009 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.freeradbiomed.2009.10.025
• 作为产物：
  描述：

  4-oxo-non-2-enal 在 rabbit 20α-hydroxysteroid dehydrogenase 、 还原型辅酶II(NADPH)四钠盐 作用下， 以 aq. phosphate buffer 为溶剂， 生成 4-oxo-2-nonenol
  参考文献：
  名称：

  兔20α-羟基类固醇脱氢酶的底物特异性和抑制剂敏感性

  摘要：

  在这项研究中，我们检查了兔20α-羟类固醇脱氢酶（AKR1C5）的底物特异性和抑制剂敏感性，该酶在孕激素失活终止妊娠中发挥作用。AKR1C5在3-酮类固醇中仅还原具有17β-或20α/β-羟基的5α-二氢类固醇的3-酮基。相比之下，该酶可逆地有效地催化各种17-和20-酮类固醇的还原，包括雌激素前体（脱氢表雄酮，雌酮和5α-雄烷-3β-ol-17-one）和解卵5β-孕烯3,20- dione。除孕激素失活外，AKR1C5的雌激素形成和生育溶性类固醇的代谢可能与其在兔分娩中的作用有关。AKR1C5还还原了各种非甾族羰基化合物，包括靛红，C型利钠肽受体和4-oxo-2-nonenal的拮抗剂，表明其在控制生物活性靛红和细胞毒性醛的解毒中的作用。AKR1C5被山茱emp醇和槲皮素等黄酮类化合物有效地和竞争性地抑制，表明其活性受摄入的黄酮类化合物的影响。

  DOI：

  10.1248/bpb.b13-00342

文献信息

• Rabbit 3-hydroxyhexobarbital dehydrogenase is a NADPH-preferring reductase with broad substrate specificity for ketosteroids, prostaglandin D2, and other endogenous and xenobiotic carbonyl compounds
  作者：Satoshi Endo、Toshiyuki Matsunaga、Atsuko Matsumoto、Yuki Arai、Satoshi Ohno、Ossama El-Kabbani、Kazuo Tajima、Yasuo Bunai、Shigeru Yamano、Akira Hara、Yukio Kitade

  DOI：10.1016/j.bcp.2013.08.024

  日期：2013.11

  for NADP(H) over NAD(H) at a physiological pH of 7.4. In the NADPH-linked reduction, 3HBD showed broad substrate specificity for a variety of quinones, ketones and aldehydes, including 3-, 17- and 20-ketosteroids and prostaglandin D(2), which were converted to 3alpha-, 17beta- and 20alpha-hydroxysteroids and 9alpha,11beta-prostaglandin F(2), respectively. Especially, alpha-diketones (such as isatin

  3-羟基己异巴比妥脱氢酶（3HBD）催化将NAD（P）（+）链接的3-羟基己异巴比妥氧化为3-羟基己异巴比妥。该酶被认为是异生物醇和某些羟基类固醇的脱氢酶，但其生理功能仍然未知。我们已经纯化了兔3HBD，分离了其cDNA，并检查了其对辅酶和底物的特异性，反应方向性和组织分布。3HBD是醛酮还原酶（AKR）超家族的成员（AKR1C29），并且在7.4的生理pH值下，NADP（H）优于NAD（H）。在与NADPH相关的还原反应中，3HBD对多种醌，酮和醛（包括3-，17-和20-酮类固醇和前列腺素D（2））显示出广泛的底物特异性，它们被转化为3alpha-，17beta-和20alpha -羟基类固醇和9alpha，11beta-前列腺素F（2），分别。特别是，α-二酮（如isatin和diacetyl）和脂质过氧化衍生的醛（如4-oxo-和4-hydroxy-2-nonenals）是显示低K（m）值（0
• Methods, compositions, and kits for improving pancreatic beta cell viability and treating diseases or conditions related to beta cell destruction
  申请人：CITY OF HOPE

  公开号：US10022403B2

  公开（公告）日：2018-07-17

  The present disclosure provides novel methods for increasing β-cell viability in islets by delivering RLIP76 polypeptides or GSTA4 polypeptides, or a combination thereof; or RLIP76 polynucleotides or GSTA4 polynucleotides, or a combination thereof, to the islets. The disclosure also provides novel methods for treating a disease or condition in a subject, such as type 1 diabetes mellitus, by delivering RLIP76 polypeptides or GSTA4 polypeptides, or a combination thereof; or RLIP76 polynucleotides or GSTA4 polynucleotides, or a combination thereof, to islets and transplanting the islets into the subject to treat the disease or condition. Kits and compositions including RLIP76 polypeptides or GSTA4 polypeptides, or a combination thereof; or RLIP76 polynucleotides or GSTA4 polynucleotides, or a combination thereof, are also provided to increase β-cell viability.

  本公开提供了通过向胰岛递送RLIP76多肽或GSTA4多肽或其组合；或RLIP76多核苷酸或GSTA4多核苷酸或其组合来提高胰岛β细胞活力的新方法。本公开还提供了治疗受试者疾病或病症（如1型糖尿病）的新方法，其方法是将RLIP76多肽或GSTA4多肽或其组合；或RLIP76多核苷酸或GSTA4多核苷酸或其组合递送至胰岛，并将胰岛移植至受试者体内以治疗疾病或病症。还提供了包括RLIP76多肽或GSTA4多肽或其组合；或RLIP76多核苷酸或GSTA4多核苷酸或其组合的试剂盒和组合物，以提高β细胞的活力。
• Characterization of rabbit aldose reductase-like protein with 3β-hydroxysteroid dehydrogenase activity
  作者：Satoshi Endo、Toshiyuki Matsunaga、Sho Kumada、Airi Fujimoto、Satoshi Ohno、Ossama El-Kabbani、Dawei Hu、Naoki Toyooka、Jun’ichi Mano、Kazuo Tajima、Akira Hara

  DOI：10.1016/j.abb.2012.07.012

  日期：2012.11

  In this study, we isolated the cDNA for a rabbit aldose reductase-like protein that shared an 86% sequence identity to human aldo-keto reductase (AKR)(1) 1B10 and has been assigned as AKR1B19 in the AKR superfamily. The purified recombinant AKR1B19 was similar to AKR1B10 and rabbit aldose reductase (AKR1B2) in the substrate specificity for various aldehydes and alpha-dicarbonyl compounds. In contrast to AKR1B10 and AKR1B2, AKR1B19 efficiently reduced 3-keto-5 alpha/beta-dihydro-C19/C21/C24-steroids into the corresponding 3 beta-hydroxysteroids, showing K-m of 1.3-9.1 mu M and k(cat) of 1.1-7.6 min(-1). The stereospecific reduction was also observed in the metabolism of 5 alpha- and 5 beta-dihydrotestosterones in AKR1B19-overexpressing cells. The mRNA for AKR1B19 was ubiquitously expressed in rabbit tissues, and the enzyme was co-purified with 3 beta-hydroxysteroid dehydrogenase activity from the lung. Thus, AKR1B19 may function as a 3-ketoreductase, as well as a defense system against cytotoxic carbonyl compounds in rabbit tissues. The molecular determinants for the unique 3-ketoreductase activity were investigated by replacement of Phe303 and Met304 in AKR1B19 with Gln and Ser, respectively, in AKR1B10. Single and double mutations (F303Q, M304S and F303Q/M304S) significantly impaired this activity, suggesting the two residues play critical roles in recognition of the steroidal substrate. (C) 2012 Elsevier Inc. All rights reserved.
• Properties and tissue distribution of a novel aldo–keto reductase encoding in a rat gene (Akr1b10)
  作者：Satoshi Endo、Toshiyuki Matsunaga、Tsukasa Kuragano、Satoshi Ohno、Yukio Kitade、Kazuo Tajima、Ossama El-Kabbani、Akira Hara

  DOI：10.1016/j.abb.2010.08.010

  日期：2010.11

  A recent rat genomic sequencing predicts a gene Akr1b10 that encodes a protein with 83% sequence similarity to human aldo-keto reductase (AKR) 1B10. In this study, we isolated the cDNA for the rat AKR1B10 (R1B10) from rat brain, and examined the enzymatic properties of the recombinant protein. R1B10 utilized NADPH as the preferable coenzyme, and reduced various aldehydes (including cytotoxic 4-hydroxy-2-hexenal and 4-hydroxy- and 4-oxo-2-nonenals) and alpha-dicarbonyl compounds (such as methylglyoxal and 3-deoxyglucosone), showing low K(m) values of 0.8-6.1 mu M and 3.7-67 mu M, respectively. The enzyme also reduced glyceraldehyde and tetroses (K(m) = 96-390 mu M), although hexoses and pentoses were inactive and poor substrates, respectively. Among the substrates, 4-oxo-2-nonenal was most efficiently reduced into 4-oxo-2-nonenol, and its cytotoxicity against bovine endothelial cells was decreased by the overexpression of R1B10. R1B10 showed low sensitivity to aldose reductase inhibitors, and was activated to approximately two folds by valproic acid, and alicyclic and aromatic carboxylic acids. The mRNA for R1B10 was expressed highly in rat brain and heart, and at low levels in other rat tissues and skin fibroblasts. The results suggest that R1B10 functions as a defense system against oxidative stress and glycation in rat tissues. (C) 2010 Elsevier Inc. All rights reserved.
• SLEEP MODULATION AGENT
  申请人：Oxford University Innovation Limited

  公开号：EP3897599A1

  公开（公告）日：2021-10-27