4-羟基-2-壬烯酸 | 139398-43-9

• 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
• 中文名称: 4-羟基-2-壬烯酸
• 英文名称: 4-hydroxy-2-nonenoic acid
• 英文别名: 1,4-dihydroxy-2-nonenal；4-hydroxynonenoic acid；4-hydroxynonenal；HNA；4-Hydroxynon-2-enoic acid
• CAS: 139398-43-9
• 化学式: C₉H₁₆O₃
• 分子量: 172.224
• InChiKey: RLNIWODKAMVILO-UHFFFAOYSA-N

物化性质

• 沸点：
  336.4±25.0 °C(Predicted)
• 密度：
  1.055±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  12
• 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：
  57.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-羟基-2-壬烯酸 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 反应 15.0h， 生成 γ-壬内酯
  参考文献：
  名称：

  Mercapturic Acid Conjugates as Urinary End Metabolites of the Lipid Peroxidation Product 4-Hydroxy-2-nonenal in the Rat

  摘要：

  4-Hydroxy-2-nonenal (HNE), an aldehyde end product of lipid peroxidation in biological systems, is capable of producing a range of powerful biological effects. Despite its biological relevance, the metabolic fate of this aldehyde is unknown in vivo. This study examines the urinary excretion of HNE in the rat and the nature of metabolites formed. Following iv administration of [H-3]HNE, the majority of the dose appeared in urine (67.1% after 48 h). The radio-HPLC metabolic profile showed that no unchanged parent compound was detected in urine whereas at least four metabolites were present, most of them corresponding to mercapturic acid conjugates. Two major pathways were involved in the biotransformation of HNE in vivo: (i) reduction/oxidation of the aldehyde group, and (ii) conjugation to endogenous glutathione leading to mercapturic acid conjugates in urine. These end products were isolated by HPLC and identified by mass spectrometry as HNE mercapturic acid, 1,4-dihydroxynonene mercapturic acid, 4-hydroxynonenoic mercapturic acid, and the corresponding lactone.

  DOI：

  10.1021/tx00043a004
• 作为产物：
  描述：

  4-羟基-2,3-壬烯醛 在 sodium chlorite 作用下， 生成 4-羟基-2-壬烯酸
  参考文献：
  名称：

  4-羟基壬烯醛（脂质过氧化的细胞毒性产物）在大鼠精确切割的肝脏切片中的代谢

  摘要：

  4-Hydroxy-2-nonenal (HNE) 是脂质过氧化的主要醛类产物，已知具有多种生物学和细胞毒性作用。研究了[4-(3)H]-HNE 的大鼠精确切割肝脏切片的体外代谢。肝切片迅速代谢 HNE-大约 85%的 0.1 microM [4-(3)H]-HNE 在 5 分钟内被降解。鉴定出的 HNE 的主要代谢物是 4-羟基壬烯酸 (HNA)、谷胱甘肽-HNE-结合物 (HNE-GSH)、谷胱甘肽-1,4-二羟基壬烯-结合物 (DHN-GSH) 和半胱氨酸-HNE-结合物 (HNE-CYS) ）。而谷胱甘肽结合表现出饱和动力学（K(m)=412.2+/-152.7 microM 和 V(max)=12.3+/-2.5 nmol h(-1) 每毫克蛋白质），海航形成是线性的高达 500 microM HNE肝脏切片。与之前的报道相比，没有 HNE、1、在本研究中检测到 4-dihydr

  DOI：

  10.1016/s0378-4274(99)00301-x

文献信息

• 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.
• Molecular characterization, expression analysis, and role of ALDH3B1 in the cellular protection against oxidative stress
  作者：Satori A. Marchitti、Chad Brocker、David J. Orlicky、Vasilis Vasiliou

  DOI：10.1016/j.freeradbiomed.2010.08.004

  日期：2010.11.15

  Aldehyde dehydrogenase (ALDH) enzymes are critical in the detoxification of aldehydes. The human genome contains 19 ALDH genes, mutations in which are the basis of several diseases. The expression, subcellular localization, enzyme kinetics, and role of ALDH3B1 in aldehyde- and oxidant-induced cytotoxicity were investigated. ALDH3B1 was purified from Sf9 cells using chromatographic methods, and enzyme kinetics were determined spectrophotometrically. ALDH3B1 demonstrated high affinity for hexanal (K-m = 62 mu M), octanal (K-m = 8 mu M), 4-hydroxy-2-nonenal (4HNE; = 52 mu M), and benzaldehyde (K-m = 46 mu M). Low affinity was seen toward acetaldehyde (K-m = 23.3 mM), malondialdehyde (K-m= 152 mM), and the ester p-nitrophenyl acetate (K-m = 3.6 mM). ALDH3B1 mRNA was abundant in testis, lung, kidney, and ovary. ALDH3B1 protein was highly expressed in these tissues and the liver. Immunofluorescence microscopy of ALDH3B1-transfected human embryonic kidney (HEK293) cells and subcellular fractionation of mouse kidney and liver revealed a cytosolic protein localization. ALDH3B1-transfected HEK293 cells were significantly protected from the lipid peroxidation-derived aldehydes trans-2-octenal, 4HNE, and hexanal and the oxidants H2O2 and menadione. In addition, ALDH3B1 protein expression was up-regulated by 4HNE in ARPE-19 cells. The results detailed in this study support a pathophysiological role for ALDH3B1 in protecting cells from the damaging effects of oxidative stress. (C) 2010 Elsevier Inc. All rights reserved.
• Quantitation of mercapturic acid conjugates of 4-hydroxy-2-nonenal and 4-oxo-2-nonenal metabolites in a smoking cessation study
  作者：Heather C. Kuiper、Brandi L. Langsdorf、Cristobal L. Miranda、Jacqueline Joss、Carole Jubert、John E. Mata、Jan F. Stevens

  DOI：10.1016/j.freeradbiomed.2009.10.025

  日期：2010.1

  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.
• Identification of Novel Urinary Metabolites of the Lipid Peroxidation Product 4-Hydroxy-2-nonenal in Rats
  作者：Jacques Alary、Laurent Debrauwer、Yvette Fernandez、Alain Paris、Jean-Pierre Cravedi、Laurence Dolo、Dinesh Rao、Georges Bories

  DOI：10.1021/tx980068g

  日期：1998.11.1

  Following iv administration of 4-hydroxy-2-nonenal (HNE) and [4-H-3]HNE to rats, 15 polar urinary metabolites accounting for about 50% of the urinary radioactivity were separated by HPLC, Among them, eight major compounds and tritiated water were quantified. The metabolites were unequivocally characterized using GC/MS and ESI/MS/MS/MS. Most of "HNE polar metabolites" originate from omega-oxidation of 4-hydroxy-2-nonenoic acid(HNA): 9-hydroxy-HNA, its mercapturic acid conjugate, and two diastereoisomers of the corresponding lactone. The oxidation of 9-hydroxy-HNA by alcohol and aldehyde dehydrogenases leads to the excretion of 9-carboxy-HNA and of the corresponding lactone mercapturic acid conjugate. 1,4-Dihydroxy-2-nonene (DHN) originating from the reduction of HNE by alcohol dehydrogenase was to a lesser extent omega-hydroxylated, leading to 9-hydroxy-DHN which was excreted as a mercapturic acid conjugate (two diastereoisomers).